Helping the Brain's Messengers Get From A to B: A First View of Shape-Shifting Movements in Membrane Transporters

Hailed as a Breakthrough in Understanding Membrane Transport, Research May Lead to Better Treatments for Depression and Substance Abuse
NEW YORK  In what has been hailed as a breakthrough, scientists from Columbia University Medical Center and Weill Cornell Medical College have outlined the molecular mechanism of membrane transport. The research shows how a protein transforms its shape to transport substances across the cell membrane in order to regulate transmission of the brain's messages across the synaptic gap from one neuron to another.
Because widely used medications for depression modulate this transport process by binding to the transporters, the new findings help explain how the medications work, and the way in which stimulants like cocaine and amphetamine produce their effects. This new understanding should also prove useful in the development of more targeted medication therapies for anxiety, depression, schizophrenia and substance abuse.
The researchers looked at transporter proteins in the family of Na+ symporters, which remove neurotransmitters from the synapse in a process called reuptake that is essential to the proper function of neural transmission. Antidepressants such as Prozac and Zoloft, which are selective serotonin reuptake inhibitors (SSRIs), and cocaine interfere with the reuptake mechanism and alter the normal exchange process between cells.
The paper describing the new findings was published in the May 13 issue of Nature and was lauded as a significant contribution to the understanding of the dynamics of the transport cycle in the journal's News & Views section. The reviewers note that until now biologists have been unable to view transporters on a single-molecule detail, but the new research "lifts the curtain and shines a spotlight onto some of the choreography" of membrane transport. In this spotlight, the new research illuminates the pathway of transported molecules revealing how transporter proteins escort ions and molecules through membranes by forming passageways in a manner the researchers liken to gates opening and closing.
"The study of membrane transport proteins and the genes that encode them offers the opportunity to investigate many aspects of disease processes. The opening and closing of the transporter 'gates' is orchestrated by binding of the transported substances and by inhibitory drugs in ways that could not be determined by previous approaches that were unable to resolve movements in individual proteins," says one senior author, Dr. Jonathan Javitch, who is the Lieber Professor of Experimental Therapeutics in the Departments of Psychiatry and Pharmacology and the Center for Molecular Recognition at Columbia University Medical Center.
Exactly how the gates open and close, and why, is not yet fully understood; however, the results from this research are an important step in that direction.
"Advances in technology have enabled cell biologists to see molecular processes at a level of detail that was not possible even in the last decade. Just as the Hubble telescope and computer-assisted tomography have allowed scientists to view objects in outer space and inside the body more clearly and in greater detail, biologists now have new tools to view what is happening at the cellular level and powerful computational methods to mimic these processes in the computer. This research has brought both advances to bear on a fundamental problem in neural transmission," says study co-author Dr. Harel Weinstein, chairman and Maxwell M. Upson Professor of Physiology and Biophysics, and director of the Institute for Computational Biomedicine (ICB) at Weill Cornell Medical College.
Dr. Weinstein credits the work of his colleague Dr. Scott Blanchard, associate professor of physiology and biophysics at Weill Cornell Medical College, in providing the expertise in a new technology that is crucial to this research. Dr. Blanchard and his team developed this new technology over numerous years and it is now at a place where functional motions of individual proteins can be directly visualized in nearly real time.
"Understanding molecular movements is important because enzyme functions hinge on motion," says Dr. Blanchard, another senior author of the new study. "To observe molecules, we attach reporter molecules called fluorophores that can be directly measured at the single-molecule scale. In so doing, motional information can be obtained about the protein to which they are linked."
In the current study, the investigators used this technique to study the LeuT transporter. They were able to monitor changes of individual molecules and reported observing two distinct states which they believe report on the open and closed states of the gating mechanism.
Dr. Weinstein notes that SSRIs were developed without a real understanding of how they work and only now researchers are beginning to understand how they bind and affect the transporters. "These medications are effective in treating many mental illnesses, including depression, obsessive-compulsive disorder and panic disorder, suggesting that these disorders have some relation to serotonin levels in the brain. Our study is the start of understanding how SSRIs work at a mechanistic level, and why they work in some people and not in others."
The study's equally contributing lead authors are Dr. Yongfang Zhao of the Center for Molecular Recognition at Columbia University Medical Center, and Daniel Terry, a graduate student in the Tri-Institutional Program in Computational Biology and Medicine at WCMC; the study is co-authored by Dr. Lei Shi of the Department of Physiology and Biophysics and the ICB, Weill Cornell Medical College.

Columbia University Medical Center

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the most comprehensive medical research enterprise in New York City and State and one of the largest in the United States. Columbia University Medical Center is affiliated with NewYork-Presbyterian Hospital, the nation's largest not-for-profit, non-sectarian hospital provider. For more information,

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston, making Weill Cornell one of only two medical colleges in the country affiliated with two U.S.News & World Report Honor Roll hospitals.

Genetic Mutations May Be Key Cause of Autism

Study Shows Changes in DNA Are Linked to Autism

Accumulation of rare DNA mutations in genes affecting brain function appears to be a major cause of autism, a large international study suggests.

"This will lead to a paradigm shift in understanding causes of autism," study researcher Stephen Scherer, PHD, of Toronto's Hospital for Sick Children, said at a news conference held to announce the findings.

Finding the cause of autism is like trying to put together a huge jigsaw puzzle with no idea of what the final picture should look like, says study researcher Anthony Monaco, MD, PhD, of the U.K.'s University of Oxford.
"What we have found are the edges of the puzzle. We now can say some of the pieces are the sky or the sand of the picture," Monaco said at the news conference. "We now see that some of the genetic changes in autism are related to connections in the brain."
The study used recently developed technology to look for unusual DNA deletions or duplications -- known as copy number variants or CNVs -- in 996 people with autism and 1,287 matched people without autism.
People with autism didn't have more CNVs than people without autism, and their CNVs weren't any bigger than usual. But in autism, CNVs are much more likely to occur in gene-containing regions of the genome.
And many of the genes in which these rare CNVs occur are linked to brain function -- especially the growth and maintenance of the synapses through which brain cells communicate with each other.
"This basically shows us that CNVs can account for a pretty appreciable percentage of autism spectrum disorder," study researcher John R. Gilbert, PhD, of the University of Miami's Institute for Human Genetics, tells WebMD.
The CNVs implicated in autism aren't all the same. In fact, the most common CNV identified in the study occurred in less than 1% of people with autism. Nearly every child studied has a unique CNV profile.
But in people with autism, CNVs cluster around networks of gene sets -- pathways -- that control brain-cell development and function. That's the paper's most important finding, says study researcher Louise Gallagher, MD, PhD, of Trinity College Dublin.
"So even if children have different genes that are influencing the development of their autism, we hope that if drug companies or biotech companies target these pathways, that the therapies might work for a broad number of the children who are affected," Gallagher said at a news conference. "Some of these therapies would still work because they act on pathways that are linked."

Autism Gene Studies: What's Next?

Studies under way are trying to link specific sets of CNVs to specific autism symptoms. Once this is done, genetic testing for CNVs could help parents identify children at high risk of autism, says study researcher Geri Dawson, PhD, of the advocacy group Autism Speaks.
"I can imagine a day when one can identify the specific genetic risk that led to an individual child's autism, and then using that genetic information to say what pathway has been affected and then choosing a medical intervention," Dawson said at the news conference.

There are no such medical treatments, although there are drugs that affect some of the pathways now linked to autism.

The new findings also shed light on the puzzling question of why children with severe autism may have brothers and sisters -- even identical twins sharing 100% of their genes -- who are unaffected.
Many of the CNVs identified in the study have what geneticists call "incomplete penetrance." This means that even if a person carries an autism-linked CNV in his or her genome, there's a chance it will have no effect.
This poses a problem for genetic testing, as children found to have autism-linked CNVs won't necessarily have autism. According to Scherer, the genes identified in the study would aid in early autism diagnosis in only about 10% of families.
Autism isn't the first disease to be linked to CNV's affecting brain function. CNV variants -- affecting some of the same pathways affected by autism-linked CNVs -- also play a role in intellectual disability (formerly called mental retardation) and schizophrenia.
Might CNVs be the long-sought factor that might make some children more susceptible to the risks posed by environmental toxins or even vaccinations?
"We do believe that environmental factors play a role in autism," Dawson said. "It is important as we continue with our science to learn how environmental factors interact with the genes we have identified here. But as of now, there is no evidence that vaccination is one of these factors."

Brain Exercises: Get Your Mind in Shape

Sorry, sudoku. The best way to stay quick-witted might be to hit the gym

When it comes to self-improvement, I’ve always prioritized my brain over my body. Why waste an hour scurrying on a treadmill like a gerbil with a bunch of sweaty strangers when I could spend it curled up with a good book? Not being one to obsess about that real or imagined “last five pounds,” I’ve never had the motivation it takes to become a regular at the gym. But I just learned something that might change my mind (in more ways than one): Exercise, far from being a boring time-suck, could actually make me smarter.

Scientists have known for some time that exercise sparks growth of new brain cells in mice, particularly in the hippocampus, the area related to memory and learning. They recently also found that it boosts the production of a protein called brain-derived neurotrophic factor (BDNF), which stimulates the rate at which nerve cells bind to create new pathways, increasing the brain’s storage capacity. Getting your body in motion gets your mind moving—both enhancing mental agility in the short term and protecting against cognitive decline in the long term. It might even benefit those with early Alzheimer’s: In a study coauthored by University of Washington behavioral sciences researcher Laura Baker, PhD, in January’s Archives of Neurology, older adults with mild cognitive impairment who engaged in regular aerobic training showed improved concentration and multitasking skills, while a control group that spent the same amount of time doing low-effort stretching exercises exhibited continued mental decline.
The best brain-boosting results come from heart-rate-raising exertion—specifically, running. In a study conducted by Charles Hillman, PhD, and published in the journal of the American College of Sports Medicine, when subjects were given memory tests both before and after 30-minute bouts of running on a treadmill, lifting weights, or sitting quietly, those who ran were significantly quicker and more accurate on the second round of tests, while the others demonstrated no change at all. “Other types of exercise, such as yoga, might have a stress-reducing meditative component,” Baker says, “but it’s aerobic exercise that seems to make the most difference to the brain.”
There are a few theories as to why this might be: One is that dramatic changes in blood flow could bring more growth factors to the brain from other parts of the body, helping to limber up connection-forming neurons, whereas with an activity such as weight-lifting, those growth factors are likely to remain in the muscles. Another is that it improves energy metabolism, ensuring that the noggin receives sufficient glucose and fuel. And a third—my favorite—is that it literally clears out the gunk that makes us dullwitted. Evidently, our brains, similar to our hearts and teeth, can suffer from a buildup of bad stuff. “Low-density lipoprotein, a cholesterol, sticks to the blood-vessel walls and inhibits the exchange of nutrients and oxygen, so theoretically the brain is not getting what it needs,” Baker says. “It’s like if we let the plumbing in our house go too long without cleaning, we get a block of water to our faucets— that’s basically what’s happening in our brains as we age. Exercise can elevate high-density lipoprotein levels, which changes the lipid profile in the brain, while at the same time forcing blood through the pipes a little faster.”
How often do we need to be hopping on the treadmill to whip our brains into the best possible shape? In general, what’s good for the heart is good for the mind: A recent Duke University study found that middle-aged subjects who worked out only 30 minutes three to four times a week and ate a healthy diet showed a 30 percent improvement in mental function after four months. “Single bouts of exercise can temporarily increase cognitive function,” Hillman says, “and data shows that getting regular exercise over time can increase both gray and white matter in the brain and make a big difference in how well you process and track information, stay on task, and allocate your mental resources.” Who wouldn’t want that? I always suspected gym devotees knew something I didn’t. Turns out, they might know a lot more.

Brain Scans Show How Meditation Calms Pain

Years of practice help users avoid anticipating discomfort, research shows

People who routinely practice meditation may be better able to deal with pain because their brains are less focused on anticipating pain, a new British study suggests.
The finding is a potential boon to the estimated 40 percent of people who are unable to adequately manage their chronic pain. It is based on an analysis involving people who practice a variety of meditation formats, and experience with meditation as a whole ranged from just a few months to several decades.

Only those individuals who had engaged in a long-term commitment to meditation were found to have gained an advantage with respect to pain relative to non-meditators.

"Meditation is becoming increasingly popular as a way to treat chronic illness such as the pain caused by arthritis," study author Dr. Christopher Brown, from the University of Manchester's School of Translational Medicine, said in a university news release.

"Recently," he noted, "a mental health charity called for meditation to be routinely available on the NHS [National Health Service of Great Britain] to treat depression, which occurs in up to 50 percent of people with chronic pain. However, scientists have only just started to look into how meditation might reduce the emotional impact of pain."

The findings were released online recently in advance of publication in an upcoming print issue of the journal Pain.

All the forms of meditation that Brown looked at included mindfulness meditation practices, which form the basis of mindfulness-based cognitive therapy, which has been recommended for recurrent depression since 2004.

By using a laser to induce pain, Brown and his team found that activity in certain parts of the brain seemed to dip when the study participants anticipated pain. With that observation he was able to establish that those with upwards of 35 years of meditation under their belt anticipated pain the least.

In particular, meditators also seemed to display unusual activity in the prefrontal cortex region of the brain that is known for regulating attention and thought processes when a person feels threatened.

"The results of the study confirm how we suspected meditation might affect the brain," explained Brown. "Meditation trains the brain to be more present-focused and therefore to spend less time anticipating future negative events. This may be why meditation is effective at reducing the recurrence of depression, which makes chronic pain considerably worse."

However, he added that "although we found that meditators anticipate pain less and find pain less unpleasant, it's not clear precisely how meditation changes brain function over time to produce these effects.

Ecstasy will damage brain

Question: Some friends invited me to a rave party. One of the boys had a pill. The drug, called “ecstasy,” was supposed to make me enjoy the fun. I trusted them. I had a great time. My friends do not seem to have any bad effects. Is it harmful?
Answer: Ecstasy damages your brain!
Repeated use of this substance harms those nerves (neurons) in the brain that release serotonin. Serotonin is a neurotransmitter that regulates memory and other thinking and emotional functions. PET scan images show markedly different and abnormal brains of people who have used ecstasy.
It enjoys a popularity at all-night raves because it has the property of providing an enduring physical stimulation.
Studies from Johns Hopkins Medical Center/National Institute of Mental Health indicate that not only is visual and verbal memory diminished but the ability to reason verbally and sustain attention is impaired.
Further, ecstasy research continues on other functions in which serotonin has been implicated, such as mood, impulse control and sleep cycles.
Animal studies, which first documented the toxic-brain effect of the drug, suggest that the loss of serotonin neurons may last for years. Brain damage is still present in monkeys seven years after ecstasy drug testing on these animals was discontinued.
Raves may sound like great fun, but if ecstasy is part of it, the cost is unthinkable.

Coventry University Hospital launches baby "brain cooling" technology

COVENTRY’S University Hospital is set to launch a state-of-the-art new service to save some of the region’s sickest babies.
The “brain cooling” technology is so new that results of the extensive trials were only published last year and it received official NHS backing last month.
It will allow doctors and nurses to wrap sick babies in special cool blankets to drop their temperature and prevent fatal brain damage.

University Hospital already has one £15,000 brain cooler and aims to buy a second with money raised by the UHCW Charity’s flagship Baby Care Appeal.
In August a team of Hollyoaks heartthrobs will take on former Coventry City and Nuneaton Borough stars to raise money for the appeal.
Dr Kate Blake, consultant neonatologist at University Hospital, said: “These machines will significantly improve a number of children’s chances of surviving as well as reducing their chances of suffering brain damage and conditions such as cerebral palsy.”
The treatment will help babies who suffer serious trauma before or during birth, perhaps because they start bleeding or because their mother’s placenta rips.
Cooling their bodies from the normal 37 degrees to 33.5 degree stops their brain swelling.
It also slows down their metabolism to stop harmful toxins being released into the blood and reaching their brain during their first three days of life.

Brain circuit 'likened to cholesterol metabolism'

A medical study has revealed that a neural circuit in the brain is directly involved in the control of cholesterol metabolism by the liver.

Published in Nature Neuroscience, the report found that inhibiting the brain's melanocortin system by pharmacological, genetic or endocrine mechanisms, increased circulating high-density lipoprotein cholesterol.

It did this by reducing its uptake by the liver, independent of food intake of body weight.

Dr Geoff Clayton, spokesperson, for the Takeheart Health Check, commented: "[It is] not surprising that the brain influences cholesterol metabolism."

However, he added that although the knowledge will add to doctors' understanding of heart disease, "it may perhaps lead to something positive but for the present it is best to stick to tried and tested methods".

The research follows a recent study conducted at the Harvard School of Public Health.

Harvard researchers found that eating processed meats lead to a higher risk of developing heart disease and diabetes.

However, no increase in the risks was found in individuals eating unprocessed red meats.

'Brain Glue' treats aneurysms

In surgery and on the table is a man who has struggled with a brain aneurysm for ten years.

Neuroradiologist Dr. Peter Pema is performing a brand new type of surgery to save his life.

Dr. Pema is going to go through the groin to seal off the aneurysm in the brain.

About one in 15 Americans suffer from aneurysms and if they rupture it can lead to stroke or even death.

Dr. Pema will use Onyx-HD 500, just approved by the FDA, in the procedure.

It's a glue for the brain.

"I put a balloon across the neck of the aneurysm, to seal the neck with a catheter in place in the aneurysm, and then inject this lava-like glue just simply to fill the whole space of the aneurysm," Dr. Pema explained.

The glue hardens and prevents ruptures that can lead to devastating bleeding and strokes.

The treatment is ideal for patients with large aneurysms that have what doctors call "wide necks" that are hard to seal off.

Faulty gene leads to protein buildup in Alzheimer's

A brain mechanism that acts like a recycling plant for toxic proteins goes haywire in people with a gene mutation linked with Alzheimer's disease, U.S. researchers said on Thursday, unveiling a discovery offering a new lead for drug companies.

They said the gene presenilin 1, which is linked to the early development of Alzheimer's, plays a role in digesting toxic proteins.
In people with Alzheimer's-related mutations, this process is faulty. Fixing it could help prevent the buildup of toxins in the brain before they do damage.
"This is cellular garbage. If the recycling factory is broken or shut down, the garbage will accumulate on the streets," said Dr. Ralph Nixon, an Alzheimer's researcher at New York University's Langone Medical Center, whose study appears in the journal Cell.
"In this case, it will accumulate in cells and eventually kill the cells," Nixon said in a telephone interview.
This new understanding of the role of a gene so closely linked with Alzheimer's disease suggests a fresh approach to drug development.
So far, researchers have focused on cleaning up the protein mess that accumulates when this brain mechanism goes awry.
These clumps made up of beta amyloid protein are considered a hallmark of Alzheimer's disease, but drugs that remove these proteins so far have not succeeded in arresting the steady decline of thinking and memory that accompanies the disease.
"We have been ignoring other pathways that may be essential to treating Alzheimer's disease. We've been basically tracking one way to approach therapy, which is to eliminate amyloid protein from the brain," Nixon said.
For the study, Nixon's team did experiments in mice genetically engineered to develop Alzheimer's disease and in skin cells of people with Alzheimer's caused by mutations in the presenilin gene. In both cases, they found the mechanism for clearing away damaged proteins was severely impaired.
"If you inhibit this clearance mechanism with drugs that block the digestive enzymes, you can produce similar types of manifestations," Nixon said.
Genetically manipulating the system so enzymes work more efficiently can improve Alzheimer's symptoms in mice, he said.
Nixon said several drug companies have expressed interest in the findings, but he would not name them.
Current drugs help manage symptoms but, so far, no treatment can stop the progression of Alzheimer's, which can start with vague memory loss and confusion before progressing to complete disability and death.
The government, private insurance and individuals spend $172 billion a year to care for people with Alzheimer's disease, the most common cause of dementia that affects 26 million people globally.
The Alzheimer's Association estimates that from 2010 to 2050, the annual cost of caring for Americans 65 and older with Alzheimer's will increase more than sixfold to $1.08 trillion.

A brain, but not as we know it

We are closer to the ultimate neurology experiment: building a brain, writes Drew Turney.
The 17th-century philosopher Rene Descartes claimed there was a disembodied driver in the brain, a kernel of intelligence that viewed sensory input and wielded consciousness to act upon it.
Though we're no closer to discovering the soul today, we know about dendrites, axons (cell components) and synapses (empty, electro-conductive space).
But what is still a mystery is how even though the brain comprises little more than these simple structures, it has somehow given rise to everything from language to love, from Beethoven to Big Brother.
Now our increasing knowledge about the brain's building blocks is bringing us closer to the ultimate neurology experiment: building one. The Blue Brain Project is one effort to create an in situ brain, using software instead of proteins in a supercomputer called Blue Gene to model the brain of a two-week-old rat. It does so by creating a 3D computer model of neurons in the neocortex (the 'intelligent' sector of the brain) where scientists can simulate the sizes, shapes, densities and electro-receptiveness of different neurons in the biological version and watch their behaviour under certain conditions.
Phase one of the Swiss Ecole Polytechnique Federale de Lausanne project (evaluation of the ''consistency and relevance of neurobiological data'') is complete, and last July the project director, Henry Markram, announced that they were 10 years away from a functional artificial human brain.
The Blue Brain Project's goal is to model the brain's response behaviour down to the nano-level. If we've programmed the way each neuron operates we can impose specific conditions like injuries or diseases that will tell us how a biological brain will behave without risk to a living patient.
Though recreating the brain is the stated aim, the Blue Brain project isn't the first neurological architecture model. As long ago as 2005 the futurist and writer Kevin Kelly claimed the internet was essentially a brain. Every computer and device can be thought of as neurons, every bit of information like the bio-electrical sparks across synapses that constantly shift, connect and disconnect to form memories, thoughts, emotions and sensory data.
Jeff Stibel, author of last year's Wired for Thought, thinks the similarities go deeper. ''The internet already has the parallel processing capability of the human mind,'' he says, ''neuroscientists call it distributed computing, where the brain's functions are distributed all over the place to happen simultaneously. The internet is a massive storage and retrieval system, and the brain's fundamental structure is roughly the same.''
This interconnectedness is also the secret to that elusive quality we call intelligence. Older scientific understanding might have convinced us to try and replicate the brain by creating a super-driver, but the true smarts might be in the network integration of a huge number of simple, low-powered processors. ''A brain is really a massive composition of mini-brains or hives,'' Stibel says. ''There's no such thing as a central decision-maker in the brain; intelligence emerges from complex parallel processing of information.''
Bill Lytton, a Blue Brain Project technical adviser, is a professor of physiology, pharmacology, biomedical engineering and neurology at New York State University. He thinks if we can perfect the mechanism to generate those hundreds of millions of base-level computations in a simulated brain, the mental commands we know as decisions, emotions or thoughts might arise as spontaneously and magically in it as they do in us.
''The simultaneous processing going on will achieve its objectives without ever bothering to reach higher levels of integration,'' he says, ''and it's not just the brain that does this - consider chickens or mice running around with their heads cut off.''
The world view of the brain as a machine packed with incredible densities of deceptively simple parts isn't new. In his 1995 book Are We Alone? cosmologist Paul Davies suggests there is no life force. The only difference between us and rocks, air or plastic might be the complexity of the structure; make something complex enough - like the proteins that form DNA - and it can be termed alive, he suggests.
So how do even start creating something so intricate it generates normal function spontaneously from the basic engineering, like expecting a 747 to take off and fly by itself just because we've built it? While a single neuron is comparatively simple it's the sheer number of types and behaviours involved that makes the computational task so big.
Another way to gain a closer understanding of the brain is to examine how it interacts with itself, as Srini Pillay does. The chief of the coaching and organisational psychology company NeuroBusiness Group and a brain imaging researcher, Pillay uses brain scanning technology to watch for changes in blood flow relative to emotion. When he prompts an emotional response in a patient or subject, the positioning and quantity of blood flow offers the possibility of regulating it to generate the mental model or mind state we want to study.
The applications of brain modelling could transform neuroscience. We can already model chemicals - most of us did so in year 7 science - if we have a virtual mock-up of how they interact at the synaptic level it would let us design better treatment for a huge range of conditions from depression to stroke.
But as we have seen, simply arranging the parts won't cause the virtual brain to just switch on. External stimulus is the key to all theoretical biology. ''We can grow neurons and support cells in culture and make them grow,'' says Richard Senelick, a neuro-rehabilitation specialist and medical director of HealthSouth Rehabilitation Institute of San Antonio in Texas, ''but we can't effectively direct them to make the correct connections consistently to reproduce function.''
The limitations of a disembodied, software-based brain don't stop there. As Bill Lytton reminds us, a real brain doesn't exist in a vacuum. ''A full brain wouldn't be all that interesting without being connected,'' he says, ''and I doubt we'd ever have the resources to build a full simulated nervous system.''
''Recent studies on heart-brain pathways illustrate that we'd need to include feedback from the heart to understand the brain more closely,'' adds NeuroBusiness Group's Srini Pillay. ''Even in the brain itself, many of the functions of brain chemicals and pathways are U-shaped. Stress, for example, may impact the brain positively up to a point, but then starts to reverse its effects. We're still trying to understand these kinds of thresholds.''
But the biggest constraint is that we simply don't know what language the brain uses to work. ''We're missing the code,'' says Lytton, who worked with the DNA pioneer Francis Crick at the Salk Institute, where the latter devoted the remainder of his career to decoding the brain.
''The brain uses different codes simultaneously to deliver information at different rates for different purposes. It's difficult to record from many neurons at once and then analyse what you've recorded. Right now we can record up to 100 but we might need to do up to 10,000.''
Of course, if we can grasp and deploy all the theory and technology we need to build a simulated brain from the ground up, there's an ever bigger philosophical question.
In her 2008 book ID, the Oxford University pharmacology professor Susan Greenfield outlines how our personalities, our hopes and dreams and our sense of self are no more than the sum total of our own neurons.
''The mind'', she writes, ''far from being some airy-fairy philosophical alternative to the biological squalor of the physical brain, is the physical brain - more specifically the personalised connectivity of that otherwise generic brain.''
If that's true and we build a human brain from scratch, what will it mean for the spiritual dimension of human life if a fully formed, sentient consciousness wakes up, shakes it computerised head and declares: ''I think, therefore I am''?

How your brain works on autopilot

Habitual learning involves two brain circuits, rat study shows

Anyone who's learned to ride a bike or touch type might have wondered how a task that is so arduous at first could be so seamlessly easy later. A new study reveals more about exactly what goes on in the brain as we form these habits, transitioning from intense concentration to autopilot.

The results, found in rats but thought to be analogous to humans, show that habitual learning, as it's called, involves two brain circuits — one used for movement and the other for higher, cognitive thinking.
As a task is learned, these circuits trade off in terms of their engagement. The movement circuit, which involves a part of the brain called the dorsolateral striatum, becomes more active, while the cognitive circuit, which involves a region called the dorsomedial striatum, takes a dip.

"If you imagine these two systems are competing, then at the end stages of training, activity in the dorsomedial striatum is fairly weak whereas activity in the dorsolateral striatum is fairly strong," said study researcher Catherine Thorn, at MIT's McGovern Institute for Brain Research. "And what we think that means is that the habit is taking over as training progresses," she told LiveScience.

While scientists had previously hypothesized these brain circuits were involved in the current work is the first to record the activity of the brain cells, or neurons, as the habits were formed. It is also the first to show that these two loops are active simultaneously.
The fact that these two circuits work together could potentially mean that one circuit might be able to compensate for the other. This would be useful in instances where one circuit is damaged, such as in Parkinson's disease, where the dorsolateral striatum is affected.

If we can learn how to tilt the competition in one direction or the other, we might help bring new focus to existing therapies, and possibly aid in the development of new therapies," said lead researcher Ann Graybiel, also of MIT. However, the researchers emphasize these sorts of applications are a long way off.

And while rat brains are good models for studying this type of learning, studies on humans are needed before scientists can know if the results apply to us.

The researchers recorded the activity of thousands of neurons in the rats' brains as they learned how to find a food reward in a maze. When they reached a specific T-junction, the rats were signaled to turn either right or left by either a sound or touch cue. Over many trials, the rats learned to associate the signal with turning in the correct direction for their reward. Eventually, this became routine.

The two brain circuits showed very different patterns of activity as the rats were learning. The dorsolateral striatal neurons (linked to motion control) were most active at specific points of action within the maze, such as a start, stop, or turn. And their activity steadily increased as the rats' performance improved, and then remained fairly stable.

On the other hand, the dorsomedial neurons (involved in higher thinking) were most active when the rats had to make the "right or left" decision. The neuron activity in this region also declined once the rats got a handle on their task. Essentially, the thinking part of the brain wasn’t so necessary as the task became routine.

"The two systems are generally simultaneously engaged, and possibly competitive, but with extended training and repetition, as the habit takes over, the dorsolateral striatum becomes more strongly activated over the dorsomedial striatum," Thorn said. 

Another hypothetical implication of the findings is that a better understanding of how these circuits interact might lead to ways to help people avoid or unlearn bad habits . "It's possible that if we could get a handle on the interaction between the two loops, we would be able to possibly suppress bad habits or encourage good ones," Thorn said. 

The results will be published June 10 in the journal Neuron.

Eating a handful of pecans daily may protect brain

Washington, June 10 (ANI): A new animal study has suggested that eating about a handful of pecans each day can protect the nervous system.

The study, conducted at the Center for Cellular Neurobiology at the University of Massachusetts Lowell, has suggested that adding pecans to your diet may delay the progression of age-related motor neuron degeneration. This may include diseases like amyotropic lateral sclerosis (ALS), also known as Lou Gehrig's Disease.


Researchers suggest vitamin E - a natural antioxidant found in pecans - may provide a key element to neurological protection shown in the study. Antioxidants are nutrients found in foods that help protect against cell damage, and studies have shown, can help fight diseases like Alzheimer's, Parkinson's, cancer and heart disease.

Pecans are the most antioxidant-rich tree nut and are among the top 15 foods to contain the highest antioxidant capacity, according to the U.S. Department of Agriculture (USDA).

"These findings suggest regular consumption of pecans may provide significant nutritive and antioxidant benefits for your body," said lead researcher Thomas B. Shea,

.Shea and his research team carried out a number of laboratory studies on three groups of mice specifically bred to demonstrate severe decline in motor neuron function that are commonly used in studies of ALS. Each of the three groups was fed a control diet or one of two diets containing differing amounts of pecans ground into their food. tandard testing methods were used to determine how well the mice scored relative to motor neuron functions, both before and after they were provided with one of the three diets.

Mice provided a diet supplemented with pecans displayed a significant delay in decline in motor function compared to mice receiving no pecans. Mice eating the diet with the most pecans (0.05 percent) fared best. Both pecan groups fared significantly better than those whose diets contained no pecans.

The study has been published in the current issue of Current Topics in Nutraceutical Research.

Brain scans reveal shopping urges

Brain scans reveal shopping urges (Getty Images)

Whether you are in a mood to shop or not, you always spend more time window-shopping than you may realise, says a new study.

The study claimed that brain scans could reveal whether someone intends to buy a product or not even when they are not consciously pondering their choices.

The ability to predict from brain scans alone what a person intends to buy could bring much-needed rigour to efforts to meld marketing and neuroscience, said Brian Knutson, a neuroscientist at Stanford University in California who was not involved in the research.
Neuromarketing, as this field is known, has been employed by drug firms, Hollywood studios and even the Campbell Soup Company to sell their wares, despite little published proof of its effectiveness.

Rather than soup, John-Dylan Haynes at the Bernstein Center for Computational Neuroscience in Berlin, Germany, attempted to predict which cars people might unconsciously favour.

For this, the researchers used functional MRI to scan the brains of two groups of male volunteers, aged 24 to 32, while they were presented with images of a variety of cars, reports New Scientist.

One group was asked to rate their impressions of the vehicles, while the second performed a distracting visual task while cars were presented in the background.

Each volunteer was then shown three cars and asked which they would prefer to buy.
The researchers found that when volunteers first viewed the car that they would subsequently "buy", specific patterns of brain activity could be seen in the brain's medial prefrontal and insula cortices - areas that are all associated with preferences and emotion.
These patterns of activity reflected the volunteers'' subsequent purchasing choice nearly three-quarters of the time, whether or not the subjects had given their undivided attention to the images of the cars when they were first shown them.

Previous studies have shown similar patterns of activity when we make explicit purchasing choices.

The new study suggests that these brain regions size up products even when we are not consciously making purchasing decisions.

The brain appears to be imparting automatic or possibly even unconscious value onto products, as soon as you're exposed to them, said Haynes.

While Knutson acknowledges that the volunteers' choices might have been different if they had been making a real decision about which car to buy, he reckons the study may still be of use to neuromarketers - specifically as a subjective way of determining whether a consumer might buy a product or not, without having to be explicitly asked.

This kind of approach might be particularly useful for inferring people's opinions of products they would be reluctant to admit to buying, said Haynes.

However, he emphasised that he is unwilling to promote neuromarketing for this purpose.

The study was published in the Journal of Neuroscience .

2 brain circuits involved with habitual learning found

There are two brain circuits involved in habitual learning, found new MIT study.
The study also found that patterns of activity in these circuits evolve as our behaviours become more habitual.
The researchers focused on the basal ganglia-brain structures that are best known for their role in movement control, but which are also involved in emotion, cognition and reward-based learning.
These different functions are thought to reside in different parts of basal ganglia. The dorsolateral part of the striatum (the input side of the basal ganglia) controls movement and is connected to the sensorimotor cortex, while the dorsomedial striatum controls flexible behaviour and is connected to higher areas known as association cortex.
But it has not been clear how these distinct circuits contribute to the learning of new behaviours.
Now for first time, researchers at MIT have recorded the activity of these two circuits in rats as they learned to navigate a maze, and found that the circuits have distinct patterns of activity that evolve during the course of learning.
The team led by Ann Graybiel recorded the activity of thousands of neurons in the striatum as rats learned to find a cache of chocolate sprinkles at the end of a maze.
As they approached a T-junction in the maze, the rats had to decide whether to turn right or left.
The correct direction was indicated by a sound or a touch cue, the meaning of which the rats had to discover through trial-and-error.
And just like human commuters, the rats performed this over and over again until the correct choice became routine.
As the rats' performance improved with repetition, the two different striatal circuits showed distinct patterns of activity.
The dorsolateral striatal neurons were most active at the specific action points within the maze (start, stop, turn etc) and this pattern became steadily stronger with practice.
The dorsomedial neurons, by contrast, showed highest activity around the decision period-when the rat experienced the cue and had to decide which way to turn.
These neurons were also most active as the rats were learning, and their activity declined in later trials once the rats had mastered the task.
"We think the two basal ganglionic circuits must work in parallel. We see what looks like competition between the two circuits until the learned behaviour becomes ingrained as a habit," said Catherine Thorn, first author of the study.
"These brain circuits are affected in Parkinson's disease, substance abuse and many psychiatric disorders. If we can learn how to tilt the competition in one direction or the other, we might help bring new focus to existing therapies, and possibly aid in the development of new therapies," said Graybiel.
But in terms of every day life, "it is good to know that we can train our brains to develop good habits and avoid bad ones," added Graybiel.

Brain vacuum technique reverses the effects of stroke

Twenty-seven stroke victims are alive and well today because of a new tool that vacuums clots out of blood vessels in the brain. Known as the Penumbra System of Continuous Aspiration Thrombectomy, the technology has been assessed at the Seaman MR Research Centre at Canada’s University of Calgary. If used within a few hours of a stroke, it can restore blood flow to the brain, thus reversing the effects of the stroke and preventing any permanent brain damage.

Medical technology firm Penumbra designed the tool. The process involves going in through the patient’s groin, and threading a tiny catheter into a blood vessel. That catheter goes up to the neck, at which point an even smaller catheter emerges from it and goes into the brain, whereupon it vacuums out the blood clot. "It requires years of training to be able to do this," said Dr. Mayank Goyal, director of the Seaman Centre. "It places enormous demands on the interventionalist, on the imaging specialists, and on the emergency team that gets the patient to a designated stroke care facility. Teamwork is key for success.”

Dr. Goyal added that the procedure will only work on massive strokes, so it is vital that patients are assessed via a CT scan as soon as possible. As revolutionary as the tool itself may be, it is of the utmost importance that medical staff are able to quickly determine which patients are candidates. To that end, Goyal is now working on a website that will help other physicians interpret CT scans accordingly.
The Penumbra System is intended for use on ischemic strokes, which involve blood clots in the brain, and constitute 80% of all strokes. Currently, such clots are treated with the drug t-PA, which has to be administered within three hours of the event. The new system involves less of a risk of bleeding, and may still work after more than three hours.

"The bottom line is we have this new technology which is extremely effective,” said Goyal. “This study involved patients with large strokes associated with much higher levels of disability and death and we have the potential to be able to give them a good quality of life."

Some Brain Cells Seem to Multitask

WEDNESDAY, June 9 (HealthDay News) -- Certain types of "multitasking" brain cells (neurons) can correctly identify a wide variety of objects, ranging from cars to cats, a new study finds.
A team at MIT's Picower Institute for Learning and Memory monitored activity in the prefrontal cortex of monkeys as they switched back and forth from distinguishing between cats vs. dogs and sports cars vs. sedans. The prefrontal cortex is the area of the brain involved in decision-making and planning.
While they did find individual neurons that were more attuned to either car images or animal images, the researchers were surprised to find that many neurons were active in both categories. In fact, these "multitasking" neurons were best at making correct identifications in both the car and animal categories.
The findings, published June 10 in the journal Neuron, suggest that cognitive demand (the amount of brain power required for a particular task) may influence whether neurons in the prefrontal cortex limit themselves to certain categories or multitask, said the researchers.
"This ability to multitask allows the brain to re-utilize the same pool of neurons for different tasks. Without it, storage capacity for critical thought might be severely limited," study author Earl K. Miller, a professor of neuroscience, said in a news release from MIT.
He added that this research could lead to a better understanding of disorders, such as autism and schizophrenia, in which people become overwhelmed by individual stimuli. For example, asking an autistic person to picture a dog may result in a flood of mental images of every dog he or she has ever seen.