Thursday, March 11, 2010

FDA: Medtronic brain stimulator missed study goal

WASHINGTON — The Food and Drug Administration said Wednesday a nerve stimulating implant from Medtronic failed to significantly reduce seizures in epilepsy patients.
Medtronic Inc., the world's largest medical device maker, has asked the FDA to approve its Deep Brain Stimulation implant for epilepsy, a neurological disease that causes seizures.
The device is already used to treat other movement disorders, including Parkinson's Disease, and more than 6,000 people in the U.S. have had the device implanted in the past decade.
But in documents posted online, the FDA said Medtronic's device failed to meet its primary study goal, which was a reduction in seizures after three months in patients with the device compared to those without it.
Medtronic attributed the missed study goal to one patient, who experienced a massive percent increase in seizures in the month after implantation.
When Medtronic excluded this patient from their analysis, the study achieved a 2.5 percent reduction in seizures. That compared to a 2.3 percent reduction in seizures when the outlier patient was included.
The FDA will ask a panel of neurologic experts on Friday whether the company's results are "clinically significant." The FDA is not required to follow the group's advice, though it often does.
The agency will also ask its experts about negative side effects reported in Medtronic's study, including depression, anxiety and memory problems.
Medtronic's Deep Brain Stimulation device is a pacemaker-shaped device surgically implanted in the chest. Wires from the device are threaded through the neck into the brain, where they stimulate areas used for coordination and movement.
The current standard of treatment for epilepsy is medication or surgery to remove parts of the brain thought to trigger seizures. However, the drugs have limited effectiveness, and some patients are too frail for brain surgery.
Rival medical device maker Cyberonics Inc. markets its own nerve stimulator for epilepsy, but many patients do not respond to the therapy.
"There is large unmet need for patients who have these terrible seizures, sometimes 50 or more a day, and they need help," said Dr. Michael Kaplitt, of New York Presbyterian Hospital. Kaplitt helped conduct Medtronic's study of the device.

How brain decodes music, lyrics

LONDON: Does the brain process lyrics and melody separately or as one? Well scientists claim to have finally found an answer to the hotly debated question.

A team at Max Planck Institute for Human Cognitive and Brain Sciences in Germany has found that the brain first deals with music and lyrics together and then, after passing through more complex processing, like understanding what lyrics mean, the two are treated separately.

The scientists studied a functional MRI brain scan of people listening to songs to make the discovery.

The team knew that when neurons process the same stimulus repeatedly, their response to it decreases over time.

They reasoned that if they varied just the tune and kept the lyrics the same, areas showing a decline in activity must be processing lyrics.

And if they varied just the lyrics, areas showing a decline must be processing the tune, while any regions declining when both the tune and lyrics are repeated must be processing both.

The team wrote four different sets of six songs and played these to 12 volunteers while scanning their brains.

In one set, all songs had different melodies and lyrics. In another, the melodies were different but lyrics were the same, while in the third set, the opposite was true. The fourth set were identical to each other.

The scientists worked out that one particular part of the brain — the superior temporal sulcus — was responding to the songs.

In the middle of the STS, the lyrics and tune were being processed as a single signal. But in anterior STS only the lyrics were processed.

How to Map the Human Brain

Mapping the connections among brain cells could someday prove as revolutionary as mapping the human genome. But tracing synaptic connections between neurons by hand has proven painstakingly slow. Bring on the computers.
Mapping the connections among brain cells could someday prove as revolutionary as mapping the human genome. But tracing each synaptic connection between neurons — essentially a manual effort so far — has proven painstakingly slow. To approach a thorough mapping, researchers will have to develop a computer-automated process.

Even the relatively simple "wiring diagram" for the tiny C. elegans worm took more than a dozen years to complete, and that involved just 302 nerve cells. The human brain presents a far greater challenge with about 100 billion neurons, and tens of trillions of synapses that represent millions of miles of wiring between neurons. (Information in the brain travels from one neuron to another across a synapse.)
"In the cerebral cortex, it's believed that one neuron is connected to 10,000 others," said Sebastian Seung, a computational neuroscientist at MIT.
Now Seung is heading a collaborative effort to speed up the mapping of the wiring diagrams, known as connectomes. He and other researchers want to train computers to imitate human tracing, so that computers can eventually create their own neuron-tracing algorithms and tackle any image of neuronal wiring,  no matter how tangled or complex.

Untangling the wires
The main challenge involves analyzing huge numbers of electron microscopic images of brain slices, and tracing the tangled connections that can extend up to several inches between neurons.

One team of neuroscientists at the Max Planck Institute for Medical Research in Heidelberg, Germany, wants to manually trace connections between neurons in the retina, or the light-sensitive tissue at the back of the eye. But as many as 10 people must trace each neuron to catch errors, out of a team of several dozen.

That manual approach would take tens of thousands of work-years to finish the connectome for just one cubic millimeter of brain, according to Viren Jain, a Max Planck Institute neuroscientist who recently finished his Ph.D. under Seung.

Another group has managed to trace the neuronal wiring that connects the brains of mice to the two small muscles that control mice ears. That involved mapping the connections from just 15 neurons branching out to reach 200 target muscle cells, but still involved a "technical tour de force to get all the wires sorted," according to Jeff Lichtman, a neuroscientist at Harvard University in Boston.

"Even though it was a very trivial exercise, it showed us something remarkable and potentially problematic," Lichtman told LiveScience.

Lichtman's success revealed a daunting reality — no single wiring diagram looked the same for any animal. The wiring diagrams for the left and right ear muscles of the same animal also looked different, despite the muscles having an identical purpose. Even a direct comparison of parallel neurons on the left and right side showed completely different branching patterns of connections.

What a brain map can tell us

Researchers have started out with mapping connections among retinas and muscles, because they represent simple challenges compared to the brain. They also know the exact purpose of the neurons and their connections in those cases.

"These things are somewhat easier to understand than if you pick randomly some place in the brain where you don't know where connections are coming from or where they're going, or what they're doing," Lichtman noted.

Neuroscientists still continue to push the boundaries of understanding without having a full wiring diagram of human or animal brains and nervous systems. But Lichtman compared having a connectome to having the human genome mapped out — each a rich data set that scientists can mine for more information.

Having a wiring diagram of the human brain might eventually help answer some fundamental questions in neuroscience, such as how information is organized in the mind. Neuroscientists might also get a better sense of how neuronal connections change over time as people age.

"Where the memory of your grandmother is stored, and in what form it is stored, is almost certainly related to how the brain cells are connected," Lichtman said.

Slicing for science
The National Institutes of Health has launched its own five-year, $30 million Human Connectome Project that starts out simple by aiming to trace the higher-level connections among brain regions, rather than every single connection. Just a few labs around the world have also begun doing their own connectome projects.

That might all change if Seung and his colleagues can truly speed up the mapping with automated computer learning.

"We will be able to test the theory — dating back to the 19th century — that memories are written in connectomes," Seung explained. "We may also be able to find connectopathies, or miswirings of the brain that cause mental disorders."

Lichtman's Harvard lab has already been working with Seung's MIT group on applying new technologies to the task. The researchers have already developed a method of slicing brains thinner than ever before, so that automated microscopes can capture images of the neuronal wiring with unprecedented high resolution.

"Every one of these technological issues is a big challenge, and especially for biologists who are more comfortable with squishy things," Lichtman said.

Boost Your Brain by Following the Heart Healthy DASH Diet

It’s no secret that eating a healthy diet and getting regular exercise are the best combination for maintaining overall health. However, by following the Dietary Approaches to Stop Hypertension (DASH) diet you can gain the added benefit of promoting heart health and maybe even boost your brain function. These are the findings of a new study from Duke University that was recently published online in Hypertension: Journal of the American Heart Association.

The DASH diet was created for the Dietary Approaches to Stop Hypertension trial, conducted by the National Heart, Lung, and Blood Institute. This was a randomized trial in which researchers analyzed the effects of diet and exercise on neurocognition among adults at risk for neurocognitive decline due to high blood pressure. Neurocognition encompasses memory, attention, and ability to learn new material. The study successfully linked exercise and diet to better cognitive function.

The purpose of the new study was to determine the impact of diet and exercise on blood pressure, while also examining the effects on cognitive function. James Blumenthal, Ph.D., lead author of the study and professor of psychology and neuroscience in the Department of Psychiatry and Behavioral Sciences at Duke University Medical Center in Durham, North Carolina said, “This study has significant implications for slowing down or even reversing age-related cognitive deficits, which may even have greater impact among people vulnerable to develop dementia or Alzheimer’s disease.”

Early Signs of Glaucoma Show up in Brain

Finding may trigger major change in how 'silent thief of sight' is treated

Experts estimate there will be 80 million cases of glaucoma worldwide by the year 2020. 

Glaucoma is the leading cause of irreversible loss of vision worldwide and now doctors believe the devastating disease begins in the brain and not in the eye as has long been thought.

Dr. David Calkins, director of research at the Vanderbilt Eye Institute in Tennessee, quotes estimates that by the year 2020, there will be 80 million cases of glaucoma worldwide.

Glaucoma is called the 'silent thief of sight,' since most people with the disease don't notice a change in their vision. It happens gradually, as increased fluid pressure inside the eye, known as ocular pressure, damages the optic nerve, which sends visual images to the brain. Damaged nerve cells cannot be replaced or repaired.

There is currently just one treatment for glaucoma, which is to reduce ocular pressure. Doctors test for glaucoma by measuring pressure inside the eye and checking peripheral vision.

But Calkins and his colleagues have discovered that the earliest signs of glaucoma are not in the eye, but in the brain.

A new understanding of the disease progression

"We don't really understand why it is that there is a loss of communication at the brain first," Calkins says, adding that it is now clear the degeneration of vision starts in the brain and works its way back to the retina, rather than the other way around.

The finding suggests that glaucoma may be reversible in the early stages, since the nerve structures between the brain and the optic nerve do not degenerate right away. "The structure that allows the communication remains in place for a very, very long time," Calkins says.

And that, he says, opens up new ways to treat glaucoma and puts it in an entirely new perspective.

"Instead of treating it just as a disease of the eye, we now understand that it is really a neurological disease that involves loss of communication between the optic nerve and the brain." And, by studying glaucoma as a neurological disease, Calkins says researchers may be able to learn more about other age-related neuro-degenerative disorders like Alzheimer's and Parkinson's disease.

The study appeared in the "Proceedings of the National Academy of Sciences."

Brain mechanism may explain alcohol cravings that drive relapse

New research provides exciting insight into the molecular mechanisms associated with addiction and relapse. The study, published by Cell Press in the March 11 issue of the journal Neuron, uncovers a crucial mechanism that facilitates motivation for alcohol after extended abstinence and opens new avenues for potential therapeutic intervention. Previous work has suggested that people, places, and objects associated with alcohol use are potent triggers for eliciting relapse and that cravings for both alcohol and drugs can increase across protracted abstinence. However, the specific molecular mechanisms that underlie pathological alcohol seeking are not well defined.
"Animal paradigms can model crucial aspects of human addiction, and these paradigms will help elucidate the molecular and cellular mechanisms that drive drug-seeking behaviors and, as a consequence, facilitate the development of novel therapeutic interventions for addiction," explains lead study author Dr. F. Woodward Hopf from the Ernest Gallo Clinic and Research Center at the University of California, San Francisco.
Dr. Hopf and colleagues were particularly interested in studying how alcohol addiction impacted a part of the brain called the nucleus accumbens (NAcb) core that is known to be important for allowing stimuli to drive motivated, goal-directed behaviors. The researchers examined the brains of rats that had experienced nearly 2 months of alcohol or sugar self-administration followed by a 3𔃃 week abstinence period.
The rats who had consumed alcohol, but not those who had consumed sugar, exhibited an increased electrical activity in the NAcb core after abstinence. The increased activity was due to an inhibition of small-conductance calcium-activated potassium channels (SK).
Importantly, pharmacological activation of SK channels produced greater inhibition of NAcb activity in the alcohol- versus sucrose-abstinent rats and significantly reduced alcohol but not sucrose seeking after abstinence. The authors concluded that decreased SK currents and increased excitability in the NAcb core represents a critical mechanism that facilitates motivation to seek alcohol after abstinence.
"Our findings are particularly exciting because the FDA-approved drug chlorzoxazone, which has been used for more than 30 years as a muscle relaxant, can activate SK channels," says Dr. Antonello Bonci, a senior author on the project. "Although SK channels are not the only target of this drug and it can present a variety of clinical side effects, it provides an unexpected and very exciting opportunity to design human clinical trials to examine whether chlorzoxazone, or other SK activators, reduce excessive or pathological alcohol drinking.