Spectrum skipping: This Motorola radio was tested by the FCC to determine whether it can find occupied frequencies of spectrum. It was also tested to determine the appropriate amount of power to use to avoid interfering with signals from television stations and wireless microphones.
Credit: Motorola

Gadgets that operate over television frequencies promise to transform the wireless landscape.

MIT Technology Review, November 2008, by Kate Greene — If you believe some radio researchers and engineers, within the next couple of years, high-bandwidth, far-reaching wireless Internet signals will soon blanket the nation. Thanks to a decision by the Federal Communications Commission (FCC) last week, megahertz frequency bands that were previously allocated to television broadcasters will be opened to other device manufacturers. The frequency liberation means that future wireless gadgets will be able to blast tens of megabits per second of data over hundreds of kilometers. They will cover previously unreachable parts of the country with Internet signals, enable faster Web browsing on mobile devices, and even make in-car Internet and car-to-car wireless communication more realistic.

The FCC announcement essentially lets wireless take advantage of unused frequencies in between channels used by broadcast television, so-called white spaces. “The announcement that the FCC will allow white-space devices has a lot of people feeling like this is a beginning of a wireless revolution,” says Anant Sahai, a professor of electrical engineering and computer science at the University of California, Berkeley.

For years, researchers have been toying with radios that are smart enough to hop from one frequency to another, leaving occupied channels undisturbed–an approach known as cognitive radio. But until the FCC made its announcement, cognitive-radio research was a purely academic pursuit. “You could do all the research you wanted on it,” Sahai says, “but it was still illegal.”

With the FCC decision, however, researchers and companies finally have the opportunity to turn prototypes into products, knowing that the gadgets could hit the market in the next couple of years. Companies including Motorola, Phillips, and Microsoft have all tested prototypes with mixed results and hope to have robust white-space devices soon.

Motorola is one of the first companies to have developed a white-space radio device that meets the basic requirements of the FCC. The device is smart enough to find and operate on free frequencies in its vicinity while controlling the strength of signals to keep them from interfering with those from other devices using nearby frequencies.

There are still lingering concerns over interference, however. This is one of the main reasons why white spaces have been off limits until now. Broadcast companies, which fund a huge lobby in Washington, were not keen on sharing their airwaves, and musicians were concerned that future white-space devices would interfere with performances using wireless microphones.

Motorola’s radio finds occupied frequencies by accessing a database of registered television stations and wireless devices within its vicinity, which it determines by using GPS. Steve Sharkey, Motorola’s policy director, notes that the device has a secondary way of finding free signals that involves just “listening” to the airwaves and scoping out free space. Sharkey believes that combining both methods will provide the best results.

Motorola’s early tests show that there’s still work to be done. During an FCC trial in October, Motorola’s device, which is about the size of a suitcase and can currently only receive signals, was able to find some but not all of the allocated frequencies in its vicinity. “These aren’t ready to go,” admits Sharkey. “They are more developmental devices, and the idea of the test is to demonstrate the basic technologies and help the FCC understand all the interactions [between transmissions].”

While eventually it may be possible to shrink down a white-space radio to the size of a cell phone, Sharkey says that Motorola is more focused on bypassing wired Internet technology by providing broadband to rural areas and providing point-to-point wireless antennas.

Other companies are more reticent to talk about their white-space plans, but Jake Ward, spokesperson for the Wireless Innovation Alliance, a consortium of companies that helped convince the FCC to open up white spaces, says that these companies have a wide range of motives. For example, computer manufacturers such as Dell may want to build broadband wireless Internet cards that are faster and have more range than existing ones do. Software companies like Microsoft could be interested in building software and applications for new devices. And an Internet giant like Google may simply want to push Internet coverage to increase the number of people who see Google ads. “Each company has its own interests,” Ward says, “but the underlying principle is that higher connectivity is better for everybody.”

Ward describes one white-space application as “mind blowing”: sending high-definition television signals from one room to another within a house. “You have a TiVo, a DVD player, a cable box, and three high-definition TVs,” he says. “Using a white-space device, you could beam those signals anywhere, to any TV.”

Of course, technical and policy challenges still remain. “Right now, a device capable of moving around to different frequencies at will is very expensive,” notes UC Berkeley’s Sahai. But he suspects that economies of scale will lead to affordable devices within the next couple of years. Additionally, he says, regulations need to be established to ensure that devices consistently avoid causing interference. Ultimately, however, Sahai sees no shortage of demand for the wireless spectrum. “If you build it better and faster and easy to deploy, then the applications will come,” he says.

Hidden wounds: Scientists used a version of MRI known as magnetic resonance spectroscopic imaging to measure the levels of two chemicals–NAA and choline–in the brains of brain-injury patients and healthy controls. In the images above, the redder the color, the higher the ratio of choline to NAA. Brain-injury patients (bottom three rows) have a higher ratio than do healthy people (top row).
Credit: Andrew Maudsley

New imaging methods may help distinguish brain damage from psychiatric disorders

MIT Technology Review, November 18, 2008, by Emily Singer — Researchers have shown that three novel imaging techniques can detect mild brain damage not visible using traditional methods. The findings will help scientists better define the type of damage that can lead to long-lasting memory and emotional problems, as well as help identify those who are most vulnerable to further trauma.

Such tools are of great interest to the military, which needs ways to distinguish traumatic brain injury from post-traumatic stress disorder. Both are common in veterans returning from Iraq and Afghanistan, and they have similar symptoms, but they require different types of treatment. The new imaging methods may also shed light on the effect of repeated mild brain trauma, such as concussion, for which soldiers and professional athletes are at risk. Anecdotal reports about ex-football players who developed early dementia, as well as concern for thousands of military troops exposed to repeated explosions, have made the long-term consequences of these types of injury an important and controversial issue.

“Right now, a football coach has no way of knowing who can go back on the field and who shouldn’t, a military officer doesn’t know who should be removed from the battlefield, a lawyer doesn’t know who has a real injury and who is faking,” says David Brody, a neurologist and scientist at Washington University, in St. Louis.

Mild traumatic brain injury is notoriously difficult to diagnose. The brains of concussion patients often look normal on CT scans, the most common test after head trauma, and “cognitive deficits can be subtle, even to a neurologist,” says Michael Selzer, a neuroscientist at the University of Pennsylvania. Fortunately, most people with concussions recover within days or weeks. But about 10 to 15 percent have persistent problems, including headaches, nausea, memory deficits, and emotional abnormalities that can linger for months or years.

Scientists hypothesize that mild head trauma damages the brain’s white matter–the long projections, called axons, that ferry messages between neurons. White matter is invisible to CT scans and magnetic resonance imaging (MRI). One of the most promising techniques for detecting subtle brain injury, called diffusion tensor imaging (DTI), is a variation of MRI that tracks water molecules in the brain’s white matter. In research presented this week at the Society for Neurosciences conference in Washington, DC, Brody and his colleagues found that DTI analysis of brain-injury patients revealed signs of white-matter damage not visible with normal MRI. The damage seemed to correlate with cognitive deficits, including slowed reaction time.

A second variation of MRI, known as magnetic resonance spectroscopic imaging (MRSI), can analyze the spectral frequencies of chemicals in the body. Andrew Maudsley and his colleagues at the University of Miami have used new advances in MRI technology, including higher-power magnets, to develop MRSI methods that can measure concentrations of two chemicals in the brain: n-acetylaspartate (NAA), a marker of white-matter density, and choline, which has been linked to injury. Previous MRSI methods yielded information only about specific brain regions, but the new technique can measure chemical concentrations across the whole brain. The researchers found decreases in NAA, possibly due to damaged axons, and increases in choline in a group of 25 patients with traumatic brain injury. “We see widespread metabolic changes, even in those with the mildest injuries,” says Maudsley, who presented the work at the conference.

A third study presented at the conference found that changes to slow-wave activity, which have been previously linked to traumatic brain injury, are likely caused by damage to the white matter. Mingxiong Huang and his colleagues used magnetoencephalography (MEG), which measures the magnetic fields produced by the electrical activity of nerve cells, to pinpoint the source of abnormal brain activity, and they discovered that it often overlapped with the location of damage detected using DTI.

While the research is promising, moving these new technologies into clinical use is likely to be a challenge. “The bar for clinical diagnosis of individual patients is different than for measuring a group effect,” says David Moore, a neurologist at Walter Reed Army Medical Center. Physicians would need to be able to detect brain changes characteristic of injury on an individual level.

Both DTI and MRSI can be performed using most standard MRI machines, but they require much more extensive data analysis than most medical imaging, something that radiologists aren’t used to providing. “It is computationally and analytically intensive,” says Brody. MEG, which is used to pinpoint seizures in epilepsy patients, is even more complicated, and the machines are still quite rare in clinical centers.

In addition, it’s not yet clear how soon after injury these approaches can identify patients likely to suffer long-term problems. While no protective treatments for brain injury yet exist, they are under development, and they would need to be delivered immediately.

Sharper image: Siemens has developed a prototype brain imager that simultaneously performs MRI and PET. The image above, taken with the new machine, shows a brain tumor (in red).
Credit: Siemens

A new imager that performs simultaneous MRI and PET scans could, among other applications, speed up the study of Alzheimer’s disease

MIT Technology Review, by Katherine Bourzac — Siemens has developed a prototype brain-imaging machine that can perform magnetic resonance imaging (MRI) and positron emission tomography (PET) simultaneously. This will save patients in clinical trials time and allow researchers to make more-accurate correlations between activity at different regions of the brain and at the cellular level. The device is the first to combine MRI, which gives information about the structure of the brain and about blood flow to brain regions, with PET, which allows researchers to monitor metabolic activity at the cellular level. The combined imaging method may help research into the basis of Alzheimer’s disease and provide a more accurate picture of drugs’ effects on the brain.

Currently, researchers must perform MRI and PET scans sequentially. “Each device only looks at part of the picture,” says Doug Darrow, director of operations for molecular imaging at Siemens. When combining the images from MRI and PET scans, researchers must make assumptions about what happened in a patient’s brain during the time elapsed between scans, and then correct for it. For example, levels of a drug in the brain might fluctuate, so the brain-activity levels pictured in an MRI image might not correlate with the concentration of a drug pictured in a PET image. A machine that combines the imaging techniques, says Darrow, gives simultaneous information about the structure and metabolism of a patient’s brain.

Darrow suggests that simultaneous PET/MRI imaging will eventually be used to help diagnose Alzheimer’s in its early stages and help doctors predict how fast a patient’s disease will progress. The system can also be used to image brain tumors.

Radiologists already use PET and MRI in clinical trials to study the changes in the brain characteristic of Alzheimer’s disease. Using specially designed chemical probes, PET allows researchers to follow the buildup of amyloid plaques, the clumps of protein that accumulate in the brain with Alzheimer’s disease. MRI allows researchers to follow the structural changes associated with the disease–such as accelerated shrinkage of the brain.

The two imaging techniques are also used to study how drugs like antidepressants operate in the human brain over time. Researchers can use functional MRI to monitor how a drug affects regional brain activity by monitoring blood flow. Using PET, they can monitor where in the brain the drug binds, and to what kind of receptors–dopamine or serotonin, for example.

Chester Mathis, professor of radiology and director of the PET facility at the University of Pittsburgh School of Medicine, cautions that the use of the combined imaging to accurately monitor the course of Alzheimer’s is still far off. But he says that his department has applied to the National Institutes of Health for funding to purchase one of the PET/MRI machines, and he does expect it to speed the pace of the researchers’ work.

Mathis says that one of the advantages of the combined imaging system is simply logistical. For patients who have Alzheimer’s disease, depression, or bipolar disorder, “getting [them] in is half the battle,” he says. Elderly and sick volunteers and their caretakers often have to go to the clinic on two different days for a PET and an MRI; each scan takes about an hour and can cause discomfort in feeble patients, who must lie still. Subjecting patients to one simultaneous scan, instead of two, would cut in half the time spent in the radiology department.

For studying the effects of pharmaceuticals on the brain, the element of time is critical, says Mathis, and performing PET and MRI scans separately means that researchers are making a lot of assumptions. Mathis suspects that, using the combined system, it will take “fewer experiments to nail down the source of pharmaceutical effects.”

Darrow says that Siemens has sent a few PET/MRI machines to researchers and is about 18 months from releasing the first commercial device. The company is also working on developing a whole-body simultaneous PET/MRI imaging system. The primary application for the whole-body system will be to search for cancerous tumors that have spread beyond their initial site.

Eye on the brain: Gene probes administered to mice via eyedrops traveled into the brain, allowing researchers to image brain damage in living animals.
Credit: Courtesy Philip Liu of Harvard Medical School

Gene probes deployed in eyedrops show brain damage in MRIs of mice.

MIT Technology Review, by Anna Davison — By dosing mice with eyedrops containing gene probes that then travel to the brain, Harvard researchers are using magnetic resonance imaging to observe the brains of living animals. The method could allow doctors to directly diagnose problems such as tumors, viral infections, and head injury, without the need for a brain biopsy. It could also be useful in monitoring patients and perhaps even targeting drug treatment to affected areas of the brain.

The gene probe technique, reported in the latest issue of the Federation of American Societies for Experimental Biology Journal, allows MRI scans that show gliosis, the process in which glial cells in the brain form a fibrous network as a defense against damage. This scarring occurs in disorders such as Alzheimer’s disease and Parkinson’s disease and as a consequence of brain tumors and serious brain injury.

The work is “really a good start,” says Monique Stins, a visiting scientist at Johns Hopkins Medical Institutions, who was not involved in the research. However, she adds, “It’s still far from the bedside. The safety of all these kinds of probes still has to be assessed.”

In earlier studies, radiologist Philip Liu and his colleagues at Harvard Medical School injected the probes directly into the brains of animals. Now they’ve incorporated them into eyedrops.

To create the gene targeting probe, Liu and his colleagues hitched a common MRI probe to a DNA sequence complementary to the mRNA of a protein found in glial cells. They tested the probe in mice in which the blood-brain barrier–which regulates the movement of substances from the blood to the brain–had been breached. The barrier is compromised in many neurological disorders, including stroke, multiple sclerosis, and viral infections, although the process is not yet well understood.

Liu and his colleagues are not sure how the probes penetrated the brain, but they believe it may have been via the lymphatic system, which includes vessels in the eyes. Fluid from the lymphatic system merges with blood in the vascular system, and if the blood-brain barrier is compromised, Liu says, probes could travel from the eye to the brain.

After treating the mice with eyedrops, the team performed MRI scans on the live animals to produce images of gliosis in their brains. Such scans could be a valuable indicator of brain injury or a neurological disorder, Liu says, and they could be performed regularly to monitor a patient’s progress.

They could also help doctors better treat patients with brain disorders or injuries, Liu says. Although gliosis performs a valuable function by isolating damaged tissue, it also hinders the brain’s repair mechanisms. “If we know gliosis is happening,” Liu says, gliosis inhibitors could be administered “to allow more time for repair.” The probes could also be used to deliver drugs directly to damaged regions of the brain, he adds.

“In theory, it’s a great concept,” says Ahmet Hoke, an associate professor of neurology and neuroscience, also at Johns Hopkins. However Hoke, who was not involved in the work, wants to see more proof that the probe is specific to gliosis.

Like Hoke, Ausim Azizi, a professor of neurology at Temple University School of Medicine, has doubts about the specificity of the probe, but he says the technique has the potential to be a useful diagnostic tool, because it could distinguish between gliomas–brain tumors that involve glial cells–and other types of tumors. However, Azizi wonders if the eyedrop method will be able to deliver enough probes to the human brain to be helpful in diagnosis.

Because the technique took advantage of breaches in the blood-brain barrier created in mice using fairly harsh techniques such as brain punctures, oxygen starvation, and electric shock, Stins says, “it remains to be seen to what extent breaches in the blood-brain barrier in human diseases will be enough to deliver this gene probe with the specificity they claim they have. They’ve got their work cut out for them.”

Why You Focus

CNN.COM, November 16, 2008 — It’s no accident that you concentrate best when you’re really engaging in something, like watching a good movie, or doing something challenging, like learning a new card game. Concentration occurs when the brain’s prefrontal cortex, which controls high-level cognitive tasks, is awash with the right cocktail of neurotransmitters, hormones, and other body chemicals, particularly the “pleasure chemical” dopamine (you get a jolt of this when you eat delicious food, have sex, or encounter something new and exciting).

Your browser may not support display of this image.”When dopamine levels rise, you subconsciously want more of the good feeling it gives you, so you’re driven to concentrate on whatever you’re doing to keep getting it,” says Lucy Jo Palladino, Ph.D., a psychologist and the author of Find Your Focus Zone. But when your attention starts to falter, your dopamine levels drop and you start looking for a new, pleasurable distraction to replace that dopamine hit.

Need one now? This mental exercise improves focus by challenging your brainpower. Take a piece of paper and two pens and sit at a table. Draw a circle with one hand and, at the same time, draw two squares with the other while tracing a circle on the floor with one foot. Not so easy, but are you feeling more focused? Read on.

It’s not only online shopping that keeps you from getting your bills paid. All of us can feel distracted when we’re at the mercy of internal factors, like fatigue, stress and anger, and external factors, like television and e-mail. Here are the most common attention zappers. Identify yours and learn how to regain your focus.

1. Lack of Sleep

When you’re tired, you’re deprived of oxygen, which is necessary for the production of chemicals, such as dopamine and adrenaline, in the prefrontal cortex. Even one night of tossing and turning can “give you symptoms that resemble ADHD (attention-deficit/hyperactivity disorder), such as forgetfulness and difficulty maintaining concentration,” says Kathleen Nadeau, Ph.D., director of the Chesapeake ADHD Center of Maryland, in Annapolis.

How to Regain Your Focus

• Get a good night’s sleep. “A good night’s sleep is like pushing the reset button in your brain,” says Edward Hallowell, M.D., author of CrazyBusy. You should try to get the amount of sleep required for you to wake up without an alarm.

• Have a snack. If you’re running on fumes and about to head into a marathon meeting, drink a glass of water and eat a snack with a balance of carbohydrates, fat, and protein, like an apple and a piece of cheese, recommends Hallowell. “This hydrates you and keeps your blood sugar levels even, both of which aid focus,” he says. And try to skip the double espresso. “Caffeine raises your adrenaline, giving you a quick burst of focus,” says Hallowell. “But if you overdo it, you’ll get the jitters, diminishing your concentration.”

Drifting off? According to Judith Greenbaum, Ph.D., a coach for people with ADHD and a coauthor of Finding Your Focus, using more than one sense (for example, seeing and hearing words) sharpens concentration.

2. Stress and Anger

When you’re tense, you get a rush of brain chemicals, like norepinephrine and cortisol, that cause you to hyperfocus “like a deer in the headlights,” says psychologist Lucy Jo Palladino. Thousands of years ago, this was a survival aid — your anxiety-induced focus helped you steer clear of potential predators. But today — when stress might feel life-threatening but usually isn’t — this only means that you have a harder time focusing on work when your mind is on your visiting in-laws or a speech you have to give. Anger has the same effect. When you’re irritated by something, your stress hormones rise and your concentration levels decrease.

How to Regain Your Focus

• Start moving. A quick burst of aerobic exercise relieves stress and improves concentration by flooding the brain with oxygen and activating brain chemicals such as dopamine. Recent studies have shown that people who engage in aerobic exercise — anything from ice-skating to taking a brisk walk — at least two days a week — have better concentration levels than do nonexercisers. If you’ve been stuck at your desk all day and a quick walk around the block isn’t an option, just stand up. This simple act tells your brain it’s time to be awake and act alert, says Kathleen Nadeau, Ph.D.

• Think happy thoughts. “Thinking of things that promote warmth, connection, and happiness reduces the hormones associated with stress, fear, and anger that can impede concentration,” says author Edward Hallowell.

MIT Technology Review, November 18, 2008. by Emily Singer — Updates from the Society for Neuroscience Conference in Washington, DC:

* Don’t Gamble When Sleep-Deprived

That may seem like obvious advice, but new research presented at the conference provides a neurological explanation for why gambling at the end of a 24-hour party binge is such a bad idea. Vinod Venkatraman and his colleagues at Duke studied volunteers as they played a specially designed gambling test, under both normal conditions and after 24 hours of sleep deprivation. Players could choose to make a risky, high-value bet; a smaller and less risky bet; or a bet that minimized potential losses. Sleep-deprived gamblers were more likely to go for the high-risk, high-reward option. Accompanying brain-imaging studies showed that these players had increased activity in the part of the brain that is linked to rewards–the same area that responds to drugs, food, and sex–and decreased activity in the part of the brain that is linked to risk aversion. No wonder casinos want to keep you gambling.

* New Drug Being Tested for Autism

Last year, Mark Bear and Gul Dolen, of MIT, published an exciting finding for the autism community: they described correcting many of the symptoms of fragile X syndrome, a genetic disorder that is the most common form of heritable mental retardation and a leading cause of autism, by changing the activity of a specific gene in mice. Drugs that target the same gene are now being tested in humans, Dolen revealed at the conference this week. This is great news, given the lack of existing or even experimental therapies for autism. Dolen declined to give further details on the tests but says she hopes that the same approach will work for more common types of autism, which do not share the gene mutation that underlies fragile X.

To correct fragile X deficits in mice, researchers started with mice that carry the mutation responsible for the disorder and show many of the same symptoms. They then engineered the mice to have lower levels of a receptor called metabotropic glutamate receptor 5 (mGluR5), which improved abnormal brain development and faulty memory and reduced seizures–some of the defining symptoms of the disorder.

Pharma companies have been developing drugs that target this class of receptors, which are involved in the brain’s primary excitatory signaling mechanism, for a number of disorders, including schizophrenia, chronic pain, Parkinson’s, and anxiety. (I wrote a piece on this new drug class several years ago but haven’t heard much about them since then. According to the NIH clinical trials database, none are in publicly funded clinical trials.) Maybe the autism findings will breathe new life into their development.

* A Mechanism Underlying the Long-Lasting Effects of Child Abuse

Epigenetics (changes in gene expression not linked to changes in DNA) is definitely a buzzword at this year’s conference. One of the most interesting presentations on this topic examines the role of epigenetics in a well-known phenomenon: the long-term impact of child abuse. Children who were abused have a much higher risk of developing a variety of mental illnesses, including schizophrenia, depression, and bipolar disorder. Tanya Roth and her colleagues at the University of Alabama, in Birmingham, found that baby mice raised by “stressed caretakers,” who mishandled and ignored their charges during the first week of life, experienced changes in gene expression and methylation of the gene for brain-derived neurotrophic growth factor into adulthood. (Methylation is the addition of methyl groups to DNA or the protein it is wrapped around, and it’s one of the major mechanisms of epigenetics. It makes DNA more tightly wound up and thus harder to transcribe.) Roth hopes that the research will allow scientists to find drugs that can reverse the changes.