High-Flying Pilots at Increased Risk of Brain Lesions

A new study suggests that pilots who fly at high altitudes may be at an increased risk for brain lesions. The study is published in the August 20, 2013, print issue of Neurology®, the medical journal of the American Academy of Neurology.

For the study, 102 U-2 United States Air Force pilots and 91 non-pilots between the ages of 26 and 50 underwent MRI brain scans. The scans measured the amount of white matter hyperintensities, or tiny brain lesions associated with memory decline in other neurological diseases. The groups were matched for age, education and health factors.

“Pilots who fly at altitudes above 18,000 feet are at risk for decompression sickness, a condition where gas or atmospheric pressure reaches lower levels than those within body tissues and forms bubbles,” said study author Stephen McGuire, MD, with the University of Texas in San Antonio, the US Air Force School of Aerospace Medicine and a Fellow of the American Academy of Neurology. “The risk for decompression sickness among Air Force pilots has tripled from 2006, probably due to more frequent and longer periods of exposure for pilots. To date however, we have been unable to demonstrate any permanent clinical neurocognitive or memory decline.”

Symptoms affecting the brain that sometimes accompany decompression sickness include slowed thought processes, confusion, unresponsiveness and permanent memory loss.

The study found that pilots had nearly four times the volume and three times the number of brain lesions as non-pilots. The results were the same whether or not the pilots had a history of symptoms of decompression sickness.

The research also found that while the lesions in non-pilots were mainly found in the frontal white matter, as occurs in normal aging, lesions in the pilots were evenly distributed throughout the brain.

“These results may be valuable in assessing risk for occupations that include high-altitude mountain climbing, deep sea diving and high-altitude flying,” McGuire said.

Computer can read letters directly from the brain

By analysing MRI images of the brain with an elegant mathematical model, it is possible to reconstruct thoughts more accurately than ever before. In this way, researchers from Radboud University Nijmegen have succeeded in determining which letter a test subject was looking at. The journal Neuroimage has accepted the article, which will be published soon. A preliminary version of the article can be read online.

Functional MRI scanners have been used in cognition research primarily to determine which brain areas are active while test subjects perform a specific task. The question is simple: is a particular brain region on or off? A research group at the Donders Institute for Brain, Cognition and Behaviour at Radboud University has gone a step further: they have used data from the scanner to determine what a test subject is looking at. The researchers ‘taught’ a model how small volumes of 2x2x2 mm from the brain scans - known as voxels - respond to individual pixels. By combining all the information about the pixels from the voxels, it became possible to reconstruct the image viewed by the subject. The result was not a clear image, but a somewhat fuzzy speckle pattern. In this study, the researchers used hand-written letters.

Prior knowledge improves model performance
‘After this we did something new’, says lead researcher Marcel van Gerven. ‘We gave the model prior knowledge: we taught it what letters look like. This improved the recognition of the letters enormously. The model compares the letters to determine which one corresponds most exactly with the speckle image, and then pushes the results of the image towards that letter. The result was the actual letter, a true reconstruction.’

‘Our approach is similar to how we believe the brain itself combines prior knowledge with sensory information. For example, you can recognise the lines and curves in this article as letters only after you have learned to read. And this is exactly what we are looking for: models that show what is happening in the brain in a realistic fashion. We hope to improve the models to such an extent that we can also apply them to the working memory or to subjective experiences such as dreams or visualisations. Reconstructions indicate whether the model you have created approaches reality.’

Improved resolution; more possibilities
‘In our further research we will be working with a more powerful MRI scanner,’ explains Sanne Schoenmakers, who is working on a thesis about decoding thoughts. ‘Due to the higher resolution of the scanner, we hope to be able to link the model to more detailed images. We are currently linking images of letters to 1200 voxels in the brain; with the more powerful scanner we will link images of faces to 15,000 voxels.’

The Concussed Brain at Work: fMRI Study Documents Brain Activation During Concussion Recovery

For the first time, researchers have documented irregular brain activity within the first 24 hours of a concussive injury, as well as an increased level of brain activity weeks later—suggesting that the brain may compensate for the injury during the recovery time.

The findings are published in the September issue of the Journal of the International Neuropsychological Society

Thomas Hammeke, PhD, professor of psychiatry and behavioral medicine at the Medical College of Wisconsin, is the lead author.  Collaborators at the Cleveland Clinic; St. Mary’s Hospital in Enid, Okl.; the University of North Carolina; Franklin College in Franklin, Ind., and the Marshfield Clinic in Marshfield, Wis., co-authored the paper.

To study the natural recovery from sports concussion, 12 concussed high school football athletes and 12 uninjured teammates were evaluated at 13 hours and again at seven weeks following concussive injury.

The concussed athletes showed the expected postconcussive symptoms, including decreased reaction time and lowered cognitive abilities. Imaging via fMRI (functional magnetic resonance imaging) showed decreased activity in select regions of the right hemisphere of the brain, which suggests the poor cognitive performance of concussion patients is related to that underactivation of attentional brain circuits.

Seven weeks post-injury, the concussed athletes showed improvement of cognitive abilities and normal reaction time. However, imaging at that time showed the post-concussed athletes had more activation in the brain’s attentional circuits than did the control athletes.

“This hyperactivation may represent a compensatory brain response that mediates recovery,” said Dr. Hammeke. “This is the first study to demonstrate that reversal in activation patterns, and that reversal matches the progression of symptoms from the time of the injury through clinical recovery.”

“Deciding when a concussed player should return to the playing field is currently an inexact science,” said Dr. Stephen Rao, director of the Schey Center for Cognitive Neuroimaging at the Cleveland Clinic and a senior author. “Measuring changes in brain activity during the acute recovery period can provide a scientific basis for making this critical decision.”

Each year, an estimated 3.8 million people sustain a traumatic brain injury (TBI). TBI is a contributing factor to a third of all injury-related deaths in the United States. More than three-quarters of the TBI’s that occur are concussions or other forms of mild TBI, many of which may go undiagnosed.

(Image: Corbis)

Why Some Remember Dreams, Others Don’t

People who tend to remember their dreams also respond more strongly than others to hearing their name when they’re awake, new research suggests.

Everyone dreams during sleep, but not everyone recalls the mental escapade the next day, and scientists aren’t sure why some people remember more than others.

To find out, researchers used electroencephalography to record the electrical activity in the brains of 36 people while the participants listened to background tunes, and occasionally heard their own first name. The brain measurements were taken during wakefulness and sleep. Half of the participants were called high recallers, because they reported remembering their dreams almost every day, whereas the other half, low recallers, said they only remembered their dreams once or twice a month.

When asleep, both groups showed similar changes in brain activity in response to hearing their names, which were played quietly enough not to wake them.

However, when awake, high recallers showed a more sustained decrease in a brain wave called the alpha wave when they heard their names, compared with the low recallers.

"It was quite surprising to see a difference between the groups during wakefulness," said study researcher Perrine Ruby, neuroscientist at Lyon Neuroscience Research Center in France.

The difference could reflect variations in the brains of high and low recallers that could have a role in how they dream, too, Ruby said.

Who remembers their dreams

A well-established theory suggests that a decrease in the alpha wave is a sign that brain regions are being inhibited from responding to outside stimuli. Studies show that when people hear a sudden sound or open their eyes, and more brain regions become active, the alpha wave is reduced.

In the study, as predicted, both groups showed a decrease in the alpha wave when they heard their names while awake. But high recallers showed a more prolonged decrease, which may be a sign their brains became more widely activated when they heard their names.

In other words, high recallers may engage more brain regions when processing sounds while awake, compared with low recallers, the researchers said.

While people are asleep, the alpha wave behaves in the opposite way —it increases when a sudden sound is heard. Scientists aren’t certain why this happens, but one idea is that it protects the brain from being interrupted by sounds during sleep, Ruby said.

Indeed, the study participants showed an increase in the alpha wave in response to sounds during sleep, and there was no difference between the groups.

One possibility to explain the lack of difference, the researchers said, could be that perhaps high recallers had a larger increase in alpha waves, but it was so high that they woke up.

Time spent awake, during the night

The researchers saw that high recallers awoke more frequently during the night. They were awake, on average, for 30 minutes during the night, whereas low recallers were awake for 14 minutes. However, Ruby said “both figures are in the normal range, it’s not that there’s something wrong with either group.”

Altogether, the results suggest the brain of high recallers may be more reactive to stimuli such as sounds, which could make them wake up more easily. It is more likely a person would remember their dreams if they are awakened immediately after one, Ruby said.

However, waking up at night can account for only a part of the differences people show in remembering dreams. “There’s still much more to understand,” she said.

The study is published online (Aug. 13) in the journal Frontiers in Psychology.

MR images showing a patient with recurrent glioblastoma responding to anti-angiogenic therapy by reduction on abnormal tumor vessel calibers and a change in the direction of the vessel vortex curve estimated from a combined gradient-echo (GE) and spin-echo (SE) MR signal readout. The change from a predominantly counter-clockwise vessel vortex direction at baseline (days -5 and -1) to a predominantly clockwise vessel vortex direction during anti-angiogenic therapy (days 1, 28, 56 and 112) indicates a dramatic transformation in vascular morphology during anti-angiogenic therapy and resulting in increased overall survival. Credit: Kyrre E. Emblem

New MR analysis technique reveals brain tumor response to anti-angiogenesis therapy

A new way of analyzing data acquired in MR imaging appears to be able to identify whether or not tumors are responding to anti-angiogenesis therapy, information that can help physicians determine the most appropriate treatments and discontinue ones that are ineffective. In their report receiving online publication in Nature Medicine, investigators from the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH), describe how their technique, called vessel architectural imaging (VAI), was able to identify changes in brain tumor blood vessels within days of the initiation of anti-angiogenesis therapy.

"Until now the only ways of obtaining similar data on the blood vessels in patients’ tumors were either taking a biopsy, which is a surgical procedure that can harm the patients and often cannot be repeated, or PET scanning, which provides limited information and exposes patients to a dose of radiation,” says Kyrre Emblem, PhD, of the Martinos Center, lead and corresponding author of the report. “VAI can acquire all of this information in a single MR exam that takes less than two minutes and can be safely repeated many times.”

Previous studies in animals and in human patients have shown that the ability of anti-angiogenesis drugs to improve survival in cancer therapy stems from their ability to “normalize” the abnormal, leaky blood vessels that usually develop in a tumor, improving the perfusion of blood throughout a tumor and the effectiveness of chemotherapy and radiation. In the deadly brain tumor glioblastoma, MGH investigators found that anti-angiogenesis treatment alone significantly extends the survival of some patients by reducing edema, the swelling of brain tissue. In the current report, the MGH team uses VAI to investigate how these drugs produce their effects and which patients benefit.

Advanced MR techniques developed in recent years can determine factors like the size, radius and capacity of blood vessels. VAI combines information from two types of advanced MR images and analyzes them in a way that distinguishes among small arteries, veins and capillaries; determines the radius of these vessels and shows how much oxygen is being delivered to tissues. The MGH team used VAI to analyze MR data acquired in a phase 2 clinical trial – led by Tracy Batchelor, MD, director of Pappas Center for Neuro-Oncology at MGH and a co-author of the current paper – of the anti-angiogenesis drug cediranib in patients with recurrent glioblastoma. The images had been taken before treatment started and then 1, 28, 56, and 112 days after it was initiated.

In some patients, VAI identified changes reflecting vascular normalization within the tumors – particularly changes in the shape of blood vessels – after 28 days of cediranib therapy and sometimes as early as the next day. Of the 30 patients whose data was analyzed, VAI indicated that 10 were true responders to cediranib, whereas 12 who had a worsening of disease were characterized as non-responders. Data from the remaining 8 patients suggested stabilization of their tumors. Responding patients ended up surviving six months longer than non-responders, a significant difference for patients with an expected survival of less than two years, Emblem notes. He adds that quickly identifying those whose tumors don’t respond would allow discontinuation of the ineffective therapy and exploration of other options.

Gregory Sorensen, MD, senior author of the Nature Medicine report, explains, “One of the biggest problems in cancer today is that we do not know who will benefit from a particular drug. Since only about half the patients who receive a typical anti-cancer drug benefit and the others just suffer side effects, knowing whether or not a patient’s tumor is responding to a drug can bring us one step closer to truly personalized medicine – tailoring therapies to the patients who will benefit and not wasting time and resources on treatments that will be ineffective.” Formerly with the Martinos Center, Sorensen is now with Siemens Healthcare.

Study co-author Rakesh Jain, PhD, director of the Steele Laboratory in the MGH Department of Radiation Oncology, adds, “This is the most compelling evidence yet of vascular normalization with anti-angiogenic therapy in cancer patients and how this concept can be used to select patients likely to benefit from these therapies.”

Lead author Emblem notes that VAI may help further improve understanding of how abnormal tumor blood vessels change during anti-angiogenesis treatment and could be useful in the treatment of other types of cancer and in vascular conditions like stroke. He and his colleagues are also exploring whether VAI can identify which glioblastoma patients are likely to respond to anti-angiogenesis drugs even before therapy is initiated, potentially eliminating treatment destined to be ineffective. A postdoctoral research fellow at the Martinos Center at the time of the study, Emblem is now a principal investigator at Oslo University Hospital in Norway and maintains an affiliation with the Martinos Center.

Researchers Gain Insight into How Ion Channels Control Heart and Brain Electrical Activity

Virginia Commonwealth University researchers studying a special class of potassium channels known as GIRKs, which serve important functions in heart and brain tissue, have revealed how they become activated to control cellular excitability.

The findings advance the understanding of the interaction between a family of signaling proteins called G proteins, and a special type of cell membrane ion pore called G protein-sensitive, inwardly rectifying potassium (GIRK) channels. The findings may one day help researchers develop targeted drugs to treat conditions of the heart such as atrial fibrillation.

In the study, published this week in the Online First section of Science Signaling, a publication of the American Association for the Advancement of Science (AAAS), researchers used a computational approach to predict the interactions between G proteins and a GIRK channel.

Rahul Mahajan, a M.D./Ph.D. candidate in the VCU School of Medicine’s Department of Physiology and Biophysics, undertook this problem for his dissertation work, under the mentorship of Diomedes E. Logothetis, Ph.D., chair of the Department of Physiology and Biophysics and the John D. Bower Endowed Chair in Physiology in the VCU School of Medicine. They developed a model and tested its predictions in cells, demonstrating how G proteins cause activation of GIRKs.  

“Malfunctions of GIRK channels have been implicated in chronic atrial fibrillation, as well as in drug abuse and addiction,” said Logothetis, who is an internationally recognized leader in the study of ion channels and cell signaling mechanisms.  

“Understanding the structural mechanism of Gβγ activation of GIRK channels could lead to rational based drug design efforts to combat chronic atrial fibrillation.”

In chronic atrial fibrillation, the GIRK channel is believed to be inappropriately open. According to Logothetis, if researchers are able to target only the specific site that keeps the channel inappropriately open, then any unrelated channels could be left unaltered, thus avoiding unwanted side effects.

Crystal structures of GIRK channels, which preceded the current study, have revealed two constrictions of the ion permeation pathway that researchers call “gates”: one at the inner leaflet of the membrane bilayer and the other close by in the cytosol, which is the liquid found inside cells.  

“The structure of the Gβγ -GIRK1 complex reveals that Gβγ inserts a part of it in a cleft formed by two cytosolic loops of two adjacent channel subunits,” Logothetis said. “This is also the place where alcohols bind to activate the channel. One can think of this cleft as a clam that has its shells either open or shut closed. Stabilization of this cleft in the ‘open’ position stabilizes the cytosolic gate in the open state.”

GIRKs are activated when they interact with G proteins coupled to receptors bound to stimulatory hormones or neurotransmitters. In heart tissue, acetylcholine released by the vagus nerve activates these channels, which hyperpolarize the membrane potential and slow heart rate. In brain tissue, GIRKs inhibit excitation by acting at postsynaptic cells.  

G proteins are composed of three subunits, a, b, and g. Since 1987, researchers have known that the Gbgsubunits directly activate the atrial GIRK channel, but an atomic resolution picture of how the two proteins interact remained elusive until now.

Moving forward, the team would like to use computational and experimental approaches to build and test the structures of the rest of the components of the G protein complex – for example, the Ga subunits and the G protein-coupled receptor – around the Gβγ-channel complex, which is the structure the team has already achieved.

8-Year-Old Never Ages, Could Reveal ‘Biological Immortality’

Gabby Williams has the facial features and skin of a newborn, and she is just as dependent. Her mother feeds, diapers and cradles her tiny frame as she did the day she was born.

The little girl from Billings, Mont., is 8 years old, but weighs only 11 pounds. Gabby has a mysterious condition, shared by only a handful of others in the world, that slows her rate of aging.

For the past two years, a doctor who has been trying to find the genetic off-switch to stop the aging process has been studying Gabby, as well as two other people who have striking similarities.

Why the ‘Benjamin Button’ children never age.

A 29-year-old Florida man has the body of a 10-year-old, and a 31-year-old Brazilian woman is the size of a 2-year-old. Like Gabby, neither seems to grow older.

Unraveling what these three people may have in common is the subject of a TLC television special, “40-Year-Old Child: A New Case,” which airs Monday, Aug. 19, at 10 p.m. ET. The show is a follow-up to Gabby’s story, which aired last year.

"In some people, something happens to them and the development process is retarded," said medical researcher Richard F. Walker. "The rate of change in the body slows and is negligible."

16-year-old is the size of a toddler.

Walker is retired from the University of Florida Medical School and now does his research at All Children’s Hospital in St. Petersburg.

"My whole career has been focused on the aging process," he told ABCNews.com. "My fixation has been not on the consequences but the cause of it."

Not only do the people he’s studying have a growth rate of one-fifth the speed of others, but they live with a variety of other medical problems, including deafness, the inability to walk, eat or even speak.

"Gabrielle hasn’t changed since pretty much forever," said her mother, Mary Margret Williams, 38. "She has gotten a little longer and we have jumped into putting her in size 3-6 month clothes instead of 0-3 months for the footies.

"Last time we weighed her she was up a pound to 11 pounds and she’s gotten a few more haircuts," she told ABCNews.com. "Other than that, she hasn’t changed much since the [2012] show."

Williams, who works part-time at a dermatologist’s office, and her husband, a corrections officer for the state, share the child care responsibilities for their perpetual infant.

Walker explains that physiological change, or what he calls “developmental inertia,” is essential for human growth. Maturation occurs after reproduction.

"Without that process we never develop," he said. "When we develop, all the pieces of our body come together and change and are coordinated. Otherwise, there would be chaos."

But, said Walker, the body does not have a “stop switch” for this development. “What happens is we become mature at age 20 and continue to change.”

The first subtle internal body changes of aging are seen in the 30s and become more visible in the 40s.

"There is a progressive erosion of internal order as a result of developmental inertia," he said.

In one of the girls Walker has studied, he found damage to one of the genes that causes developmental inertia, a finding that he said is significant. He also suspects the mutations are on the regulatory genes on the second female X chromosome.

"If we could identify the gene and then at young adulthood we could silence the expression of developmental inertia, find an off-switch, when you do that, there is perfect homeostasis and you are biologically immortal."

Now Walker doesn’t mean that people will never die. Disease and accidents will still end human life.

"But you wouldn’t have the later years — you’d remain physically and functionally able," he said.

That is why he believes his study of Gabby Williams’ genetic code is so important. “She fits the model,” said Walker.

"We’ve been on this journey to find out, are my other children at any risk in having a child like Gabrielle," said Williams, who has five other children between the ages of 1 and 10.

"We did find out with Dr. Walker when he did the [gene] sequencing that it’s not something we can pass on but just an abnormality, a mutated gene that was just happenstance," she said. "That was a relief for us."

At first, when the Williams family members found out about Walker’s research, they hesitated to become guinea pigs in the studies that would promote a so-called “fountain of youth.”

"There was some concern," she said. "We are good Catholics, God-fearing people and we believe we are meant to get old — the process of life — and meant to die. It was scary to think about, and we did not want to be part of it."

But as they talked further with Walker, the family realized that his research was designed to help people struggling with the impairments of old age.

"Alzheimer’s is one of the scariest diseases out there," said Williams. "If what Gabrielle holds inside of her would find a cure — for sure we would be a part of the research project. We have faith that Dr. Walker and the scientific community do find something focused more on the disease of aging, rather than making you 35 for the rest of your life."

As for Gabby’s life span, her doctors cannot say what that will look like.

"From the time of her birth, we didn’t think she would be with us very long," said her mother. "The fact is she is now going on 9 years. She kind of surpassed my expectations from the get go.

"It’s not something I worry about," said Williams, who said she trusts that God has a plan for her infantile daughter.

"When he is ready to take her back, it will be sad," she said. "But what a glorious thing it will be for Gabby to go to heaven one day. I know it will happen, but I am not hoping it’s any day soon."