Neuroscientists show ’jumping genes’ may contribute to aging-related brain defects

As the body ages, the physical effects are notable; wrinkles in the skin appear, physical exertion becomes harder. But there are also less visible processes going on. Inside aging brains there is another phenomenon at work, which may contribute to age-related brain defects.

In a paper published in the journal Nature Neuroscience CSHL Associate Professor Joshua Dubnau and colleagues show that so-called “jumping genes,” or transposons, increase in abundance and activity in the brains of fruit flies as they age.

Originally discovered at CSHL by Professor Barbara McClintock while working on maize (corn) in the 1940s, transposons are typically repeat DNA sequences that insert themselves into the DNA of an animal or plant.

The moniker “jumping genes” comes from the fact that when activated they can reinsert themselves, or transpose, into another part of the genome. In the course of doing so they are thought to either provide variations in genetic function or, especially in the germline, induce potentially fatal disruptive defects.

Jumping genes in the brains of fruit flies

The median lifespan of a fruit fly can be measured in days. The average fly lives for somewhere between 40-50 days. But they provide a powerful model with which to get at the genetics of things like aging and brain function, including memory.

Dubnau’s interest was piqued by an experiment in which his team showed that when the activity of a protein called Ago2 (Argonaute 2) was perturbed, so was long-term memory—which was tested using a trained Pavolvian response to smell. “This is a neurodegenerative defect that gets profoundly more apparent with age of the flies,” notes Dubnau.

Since Ago2 is known to be involved in protecting against transposon activity in fruit flies, Dubnau and colleagues in his lab, including Wanhe Li and Lisa Prazak, were compelled to look for transposons.

Though transposons have been shown to be active during normal brain development, they are silenced soon afterward. The implication is that they have some functional role in development.

When Dubnau’s group looked for transposons they found that there is a marked increase in transposon levels in the brain cells, or neurons, by 21 days of age in normal fruit flies. The levels were observed to increase steadily with age. These transposons, including one in particular called gypsy, were highly active, jumping from place to place in the genome.

When they blocked Ago2 from being expressed in fruit flies, transposons accumulated at a much younger age. In fact the levels of transposons in young Ago2 “knock-out” flies were equivalent to those in much older normal flies, and increased further still as the Ago2 knock-out flies aged.

Accompanying this transposon accumulation were defects in long-term memory that mirrored those usually seen in much older flies, as well as a much-reduced lifespan. “Essentially the Ago2 knock out flies have no long-term memory by the time they are 20 days old, while normal flies have a normal long-term memory at the same age,” Dubnau reports.

In a previous paper the Dubnau lab, in collaboration with CSHL Assistant Professor Molly Hammell, established a connection between transposons and devastating neurodegenerative diseases such ALS (amyotrophic lateral sclerosis, or Lou Gehrig’s disease) and FTLD (frontotemporal lobar degeneration). The link was the protein TDP-43, which they showed controls transposon activity.

Taken together with the results in his team’s new paper, Dubnau proposes that a “transposon storm” may be responsible for age-related neurodegeneration as well as the pathology seen in some neurodegenerative disorders.

However, his studies so far don’t address whether transposons are the cause or an effect of aging-related brain defects. “The next step will be to activate transposons by genetically manipulating fruit flies and ask whether they are a direct cause of neurodegeneration,” Dubnau says.

Non-Invasive Mapping Helps to Localize Language Centers Before Brain Surgery

A new functional magnetic resonance imaging (fMRI) technique may provide neurosurgeons with a non-invasive tool to help in mapping critical areas of the brain before surgery, reports a study in the April issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

Evaluating brain fMRI responses to a “single, short auditory language task” can reliably localize critical language areas of the brain—in healthy people as well as patients requiring brain surgery for epilepsy or tumors, according to the new research by Melanie Genetti, PhD, and colleagues of Geneva University Hospitals, Switzerland.

Brief fMRI Task for Functional Brain Mapping
The researchers designed and evaluated a quick and simple fMRI task for use in functional brain mapping. Functional MRI can show brain activity in response to stimuli (in contrast to conventional brain MRI, which shows anatomy only). Before neurosurgery for severe epilepsy or brain tumors, functional brain mapping provides essential information on the location of critical brain areas governing speech and other functions.

The standard approach to brain mapping is direct electrocortical stimulation (ECS)—recording brain activity from electrodes placed on the brain surface. However, this requires several hours of testing and may not be applicable in all patients. Previous studies have compared fMRI techniques with ECS, but mainly for determining the side of language function (lateralization) rather than the precise location (localization).

The new fMRI task was developed and evaluated in 28 healthy volunteers and in 35 patients undergoing surgery for brain tumors or epilepsy. The test used a brief (eight minutes) auditory language stimulus in which the patients heard a series of sense and nonsense sentences.

Functional MRI scans were obtained to localize the brain areas activated by the language task—activated areas would “light up,” reflecting increased oxygenation. A subgroup of patients also underwent ECS, the results of which were compared to fMRI.

Non-invasive Test Accurately Localizes Critical Brain Areas
Based on responses to the language stimulus, fMRI showed activation of the anterior and posterior (front and rear) language areas of the brain in about 90 percent of subjects—neurosurgery patients as well as healthy volunteers. Functional MRI activation was weaker and the language centers more spread-out in the patient group. These differences may have reflected brain adaptations to slow-growing tumors or longstanding epilepsy.

Five of the epilepsy patients also underwent ECS using brain electrodes, the results of which agreed well with the fMRI findings. Two patients had temporary problems with language function after surgery. In both cases, the deficits were related to surgery or complications (bleeding) in the language area identified by fMRI.

Functional brain mapping is important for planning for complex neurosurgery procedures. It provides a guide for the neurosurgeon to navigate safely to the tumor or other diseased area, while avoiding damage to critical areas of the brain. An accurate, non-invasive approach to brain mapping would provide a valuable alternative to the time-consuming ECS procedure.

"The proposed fast fMRI language protocol reliably localized the most relevant language areas in individual subjects," Dr. Genetti and colleagues conclude. In its current state, the new test probably isn’t suitable as the only approach to planning surgery—too many areas "light up" with fMRI, which may limit the surgeon’s ability to perform more extensive surgery with necessary confidence. The researchers add, "Rather than a substitute, our current fMRI protocol can be considered as a valuable complementary tool that can reliably guide ECS in the surgical planning of epileptogenic foci and of brain tumors."

Mind over matter? Study led by NUS researcher reveals for the first time that core body temperature can be controlled by the brain

A team of researchers led by Associate Professor Maria Kozhevnikov from the Department of Psychology at the National University of Singapore (NUS) Faculty of Arts and Social Sciences showed, for the first time, that it is possible for core body temperature to be controlled by the brain. The scientists found that core body temperature increases can be achieved using certain meditation techniques (g-tummo) which could help in boosting immunity to fight infectious diseases or immunodeficiency.

Published in science journal PLOS ONE in March 2013, the study documented reliable core body temperature increases for the first time in Tibetan nuns practising g-tummo meditation. Previous studies on g-tummo meditators showed only increases in peripheral body temperature in the fingers and toes. The g-tummo meditative practice controls “inner energy” and is considered by Tibetan practitioners as one of the most sacred spiritual practices in the region. Monasteries maintaining g-tummo traditions are very rare and are mostly located in the remote areas of eastern Tibet.

The researchers collected data during the unique ceremony in Tibet, where nuns were able to raise their core body temperature and dry up wet sheets wrapped around their bodies in the cold Himalayan weather (-25 degree Celsius) while meditating. Using electroencephalography (EEG) recordings and temperature measures, the team observed increases in core body temperature up to 38.3 degree Celsius. A second study was conducted with Western participants who used a breathing technique of the g-tummo meditative practice and they were also able to increase their core body temperature, within limits.

Applications of the research findings

The findings from the study showed that specific aspects of the meditation techniques can be used by non-meditators to regulate their body temperature through breathing and mental imagery. The techniques could potentially allow practitioners to adapt to and function in cold environments, improve resistance to infections, boost cognitive performance by speeding up response time and reduce performance problems associated with decreased body temperature.

The two aspects of g-tummo meditation that lead to temperature increases are “vase breath” and concentrative visualisation. “Vase breath” is a specific breathing technique which causes thermogenesis, which is a process of heat production. The other technique, concentrative visualisation, involves focusing on a mental imagery of flames along the spinal cord in order to prevent heat losses. Both techniques work in conjunction leading to elevated temperatures up to the moderate fever zone.

Assoc Prof Kozhevnikov explained, “Practicing vase breathing alone is a safe technique to regulate core body temperature in a normal range. The participants whom I taught this technique to were able to elevate their body temperature, within limits, and reported feeling more energised and focused. With further research, non-Tibetan meditators could use vase breathing to improve their health and regulate cognitive performance.”

Further research into controlling body temperature

Assoc Prof Kozhevnikov will continue to explore the effects of guided imagery on neurocognitive and physiological aspects. She is currently training a group of people to regulate their body temperature using vase breathing, which has potential applications in the field of medicine. Furthermore, the use of guided mental imagery in conjunction with vase breathing may lead to higher body temperature increases and better health.

Researchers shine light on how stress circuits learn

Researchers at the University of Calgary’s Hotchkiss Brain Institute have discovered that stress circuits in the brain undergo profound learning early in life. Using a number of cutting edge approaches, including optogenetics, Jaideep Bains, PhD, and colleagues have shown stress circuits are capable of self-tuning following a single stress. These findings demonstrate that the brain uses stress experience during early life to prepare and optimize for subsequent challenges.

The team was able to show the existence of unique time windows following brief stress challenges during which learning is either increased or decreased. By manipulating specific cellular pathways, they uncovered the key players responsible for learning in stress circuits in an animal model. These discoveries culminated in the publication of two back-to-back studies in the April 7 online edition of Nature Neuroscience [1, 2], one of the world’s top neuroscience journals.

"These new findings demonstrate that systems thought to be ‘hardwired’ in the brain, are in fact flexible, particularly early in life," says Bains, a professor in the Department of Physiology and Pharmacology. "Using this information, researchers can now ask questions about the precise cellular and molecular links between early life stress and stress vulnerability or resilience later in life."

Stress vulnerability, or increased sensitivity to stress, has been implicated in numerous health conditions including cardiovascular disease, obesity, diabetes and depression. Although these studies used animal models, similar mechanisms mediate disease progression in humans.

"Our observations provide an important foundation for designing more effective preventative and therapeutic strategies that mitigate the effects of stress and meet society’s health challenges," he says.

Brain Games are Bogus

A decade ago, a young Swedish researcher named Torkel Klingberg made a spectacular discovery. He gave a group of children computer games designed to boost their memory, and, after weeks of play, the kids showed improvements not only in memory but in overall intellectual ability. Spending hours memorizing strings of digits and patterns of circles on a four-by-four grid had made the children smarter. The finding countered decades of psychological research that suggested training in one area (e.g., recalling numbers) could not bring benefits in other, unrelated areas (e.g., reasoning). The Klingberg experiment also hinted that intelligence, which psychologists considered essentially fixed, might be more mutable: that it was less like eye color and more like a muscle.

It seemed like a breakthrough, offering new approaches to education and help for people with A.D.H.D., traumatic brain injuries, and other ailments. In the years since, other, similar experiments yielded positive results, and Klingberg helped found a company, Cogmed, to commercialize the software globally. (Pearson, the British publishing juggernaut, purchased it in 2010.) Brain training has become a multi-million-dollar business, with companies like Lumosity, Jungle Memory, and CogniFit offering their own versions of neuroscience-you-can-use, and providing ambitious parents with new assignments for overworked but otherwise healthy children. The brain-training concept has made Klingberg a star, and he now enjoys a seat on an assembly that helps select the winners of the Nobel Prize in Physiology or Medicine. The field has become a staple of popular writing. Last year, the New York Times Magazine published a glowing profile of the young guns of brain training called “CAN YOU MAKE YOURSELF SMARTER?”

The answer, however, now appears to be a pretty firm no—at least, not through brain training. A pair of scientists in Europe recently gathered all of the best research—twenty-three investigations of memory training by teams around the world—and employed a standard statistical technique (called meta-analysis) to settle this controversial issue. The conclusion: the games may yield improvements in the narrow task being trained, but this does not transfer to broader skills like the ability to read or do arithmetic, or to other measures of intelligence. Playing the games makes you better at the games, in other words, but not at anything anyone might care about in real life.

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State science fair winner creates robot

The winner of this year’s State Science and Engineering Fair is from South Florida, and her project can someday make life easier for the physically challenged.

"It captures the brain waves of electrochemical activity. Basically, the nerve impulse produced by the brain, and it sends it over to the robot," said Daniela Rodriguez.

Steve is an award winning robot controlled by brain waves. He was invented by 13-year-old Daniela Rodriguez, who loves math and science. “I’ve always been interested in robotics; it’s my passion,” she said.

This year, Rodriguez won first place in the Annual State Science and Engineering Fair against 900 other finalists.

Rodriguez’ goal is to help people. “If the person is disabled, they can sit in their wheelchair, and they can use their thoughts and brain waves to control its movements, so they don’t have to move,” she said.

Her science project comes from the heart. Her mother was diagnosed with multiple sclerosis in 1996, and she is trying to find a way to keep her mom independent. “I work really hard to try to stay mobile, but the fact that she wants to help patients dealing with this illness is just a Godsend” said Rodriguez’ mom Jeannie.

Rodriguez’ wants to one day use her technology to help paralyzed people. Steve’s technology can even give wounded veterans the ability to use their brains to move the robot. “To help them move around in their wheelchairs or move their prosthetics because usually prosthetics now is just the muscle movement, but now it can be used and be more natural. It’s moving by your brain,” said Rodriguez.

Not only is Rodriguez winning awards, prosthetic companies have expressed interest in her program.

Scientists discover how brains change with new skills

The phrase “practice makes perfect” has a neural basis in the brain. Researchers have discovered a set of common changes in the brain upon learning a new skill. They have essentially detected a neural marker for the reorganization the brain undergoes when a person practices and become proficient at a task.

Successful training not only prompts skill-specific changes in the brain, but also more global changes that are consistent across many different types of skills training, the researchers report in the journal Neurorehabilitation and Neural Repair. Their results indicate that as you become more adept at a skill, your brain no longer needs to work as hard at it. The brain, they report, shifts from more controlled to more automatic processing as a skill is learned, regardless of the specific type of training, they said.

“The training-related changes we found – that signify a shift to a more ‘efficient’ configuration of brain networks – provide a potential new brain marker for training effectiveness,” said neuroscientist Nathan Spreng, assistant professor of human development and the Rebecca Q. and James C. Morgan Sesquicentennial Faculty Fellow in Cornell’s College of Human Ecology. “Such neural markers are increasingly being used to inform the design of new or more-targeted interventions to improve cognitive and motor functioning in aging, brain injury or disease,” he added.

The study is the most comprehensive review of the neural correlates of training to date and the first to associate training with alterations in large-scale brain networks, said Spreng, who was awarded the distinction of “rising star” in March by the Association for Psychological Science.

The researchers conducted a systematic meta-analysis of 38 neuroimaging studies of cognitive and motor skills training interventions in healthy young adults – more than 500 participants in all. Using a quantitative literature review method, they analyzed functional neuroimaging data and mapped the patterns of brain activity changes before and after the training across the individual experiments.

The researchers found that the brain regions that are involved in attention-demanding activities are less active after training compared with before, whereas the brain regions that typically are at rest (known as the default network), became more active.

Specifically, training resulted in decreased activity in brain regions involved in effortful control and attention that closely overlap with the frontoparietal control and dorsal attention networks. Increased activity was found after training, however, in the default network that is involved in self-reflective activities, including future planning or even day dreaming. Thus, skill mastery is associated with increased activity in areas not engaged in skill performance, and this shift can be detected in the large-scale networks of the brain.

“The power of meta-analysis methods to systematically and quantitatively review neuroimaging studies makes possible discoveries such as ours that can provide new insights into how the brain functions; this helps us lay the foundation for better treatments of brain disorders in the future,” said Spreng.

“There have now been over 100,000 neuroimaging papers published, so these types of meta-analytic reviews offer new opportunities to identify common patterns of brain activity across a larger and more diverse array of studies,” he added.

(Image: iStockphoto)

Shift of Language Function to Right Hemisphere Impedes Post-Stroke Aphasia Recovery

In a study designed to differentiate why some stroke patients recover from aphasia and others do not, investigators have found that a compensatory reorganization of language function to right hemispheric brain regions bodes poorly for language recovery. Patients who recovered from aphasia showed a return to normal left-hemispheric language activation patterns. These results, which may open up new rehabilitation strategies, are available in the current issue of Restorative Neurology and Neuroscience.

“Overall, approximately 30% of patients with stroke suffer from various types of aphasia, with this deficit most common in stroke with left middle cerebral artery territory damage. Some of the affected patients recover to a certain degree in the months and years following the stroke. The recovery process is modulated by several known factors, but the degree of the contribution of brain areas unaffected by stroke to the recovery process is less clear,” says lead investigator Jerzy P. Szaflarski, MD, PhD, of the Departments of Neurology at the University of Alabama and University of Cincinnati Academic Health Center.

For the study, 27 right-handed adults who suffered from a left middle cerebral artery infarction at least one year prior to study enrollment were recruited. After language testing, 9 subjects were considered to have normal language ability while 18 were considered aphasic. Patients underwent a battery of language tests as well as a semantic decision/tone decision cognitive task during functional MRI (fMRI) in order to map language function. MRI scans were used to determine stroke volume.

The authors found that linguistic performance was better in those who had stronger left-hemispheric fMRI signals while performance was worse in those who had stronger signal-shifts to the right hemisphere. As expected, they also found a negative association between the size of the stroke and performance on some linguistic tests. Right cerebellar activation was also linked to better post-stroke language ability.

The authors say that while a shift to the non-dominant right hemisphere can restore language function in children who have experienced left-hemispheric injury or stroke, for adults such a shift may impede recovery. For adults, it is the left hemisphere that is necessary for language function preservation and/or recovery.