'Microlesions' in epilepsy discovered by novel technique

Clusters of differentially expressed genes predict cellular abnormalities. Credit: Jeffrey Loeb

Using an innovative technique combining genetic analysis and mathematical modeling with some basic sleuthing, researchers have identified previously undescribed microlesions in brain tissue from epileptic patients. The millimeter-sized abnormalities may explain why areas of the brain that appear normal can produce severe seizures in many children and adults with epilepsy.

The findings, by researchers at the University of Illinois at Chicago College of Medicine, Wayne State University and Montana State University, are reported in the journal Brain.

Epilepsy affects about 1 percent of people worldwide. Its hallmark is unpredictable seizures that occur when groups of neurons in the brain abnormally fire in unison. Sometimes epilepsy can be traced back to visible abnormalities in the brain where seizures start, but in many cases, there are no clear abnormalities or scaring that would account for the epileptic activity.

"Understanding what is wrong in human brain tissues that produce seizures is critical for the development of new treatments because roughly one third of patients with epilepsy don't respond to our currently available medications," said Dr. Jeffrey Loeb, professor and head of neurology and rehabilitation in the UIC College of Medicine and corresponding author on the study. "Knowing these microlesions exist is as huge step forward in our understanding of human epilepsy and present new targets for treating this disease."

Loeb and colleagues searched for cellular changes associated with epilepsy by analyzing thousands genes in tissues from 15 patients who underwent surgery to treat their epilepsy. They used a mathematical modeling technique called cluster analysis to sort through huge amounts of genetic data.

Using the model, they were able to predict and then confirm the presence of tiny regions of cellular abnormalities -- the microlesions -- in human brain tissue with high levels of epileptic electrical activity, or 'high-spiking' areas where seizures begin.

"Using cluster analysis is like using a metal detector to find a needle in a haystack," said Loeb. The model, he said, revealed 11 gene clusters that "jumped right out at us" and were either up-regulated or down-regulated in tissue with high levels of epileptic electrical activity compared to tissue with less epileptic activity from the same patient.

When they matched the genes to the types of cells they came from, the results predicted that there would be reductions of certain types of neurons and increases in blood vessels and inflammatory cells in brain tissue with high epileptic activity.

When Fabien Dachet, an expert in bioinformatics research at UIC and first author of the study, went back to the tissue samples and stained for these cells, he found that all of the prediction were correct- there was a marked increase in blood vessels, inflammatory cells, and there were focal microlesions made up of neurons that had lost most of their normal connections that allow them to communicate with one another. "We think that these newly found microlesions lead to spontaneous, abnormal electrical currents in the brain that lead to epileptic seizures," said Loeb.

Loeb and his colleagues at UIC are using the same approach to look for the clusters of differentially expressed genes associated with ALS, a neurodegenerative disease, and in brain tumors. "We now have a way to predict cellular changes by simply measuring the genetic composition, with some fairly simple calculations, between more- and less-affected epileptic human tissues," explained Loeb.

"This technique gives us the ability to discover previously unknown cellular abnormalities in almost any disease where we have access to human tissues," Loeb said. He is currently developing at UIC a national 'neurorepository' of electrically mapped and genetically analyzed brain tissue for such studies.

Source: University of Illinois at Chicago

Wearable device to track diet under development

A concept of the device with sensor was made through 3-D printing. Credit: The University of Alabama

Sensors and software used to track physical activity are increasingly popular, as smart phones and their apps become more powerful and sophisticated, but, when it comes to food, they all rely on the user to report meals.

Dr. Edward Sazonov, an associate professor of electrical and computer engineering at The University of Alabama, hopes to change that through development of a sensor worn around the ear that would automatically track diet, giving medical professionals and consumers accurate information that can be missed with self-reporting.

"Weight gain comes from an unbalance of the energy we take in versus the energy we expend," Sazonov said. "We can estimate diet and nutrient intake, but the primary method is self-reporting. The sensor could provide objective data, helping us better understand patterns of food intake associated with obesity and eating disorders."

Sazonov is the lead on a $1.8 million, five-year grant from the National Institute of Health to test the practical accuracy of the wearable sensor in tracking diet. Already proven viable, the device will be updated, further miniaturized and validated in a more formal, robust experiment in the community.

Called an Automatic Ingestion Monitor, or AIM, it has potential to monitor eating by automatically detecting and capturing imagery of food intake and to estimate the mass and the energy content of ingested food.

The sensor feels vibrations from movement in the jaw during food intake, and the device is programmed to filter out jaw motions, such as talking, that are not coming from drinking or eating. Estimates of energy intake would be taken from the pictures of food or drink.

More than two-thirds of adults in the United States are clinically overweight or obese, according to estimates from the Center for Disease Control and Prevention.

"Eating may be an unconscious, even automatic behavior for some individuals, and the literature is full of examples of dietary behaviors which increase the risk for overeating," Sazonov said.

In a study, the AIM will be tested against the accuracy of an alternative method, the use of a doubly-labeled water to track energy use by humans. That method measures the body's elimination rate of stable isotopes of hydrogen and oxygen added to the water, a process that can take two weeks. The information can be used to estimate how many calories a person consumes over a period of time.

However, this method is expensive and requires medical specialization, and, unlike the proposed AIM, does not track eating behavior.

The information provided by AIM could be used to improve behavioral weight loss strategies or to develop new kinds of weight-loss interventions. In addition, the AIM could also provide an objective method of assessing the effectiveness of pharmacological and behavioral interventions for eating disorders.

It's likely the technology's first application would be as a medical device, but Sazonov said it's possible it could become a consumer device that would eliminate the need for health-conscious people to keep a record of their diet.

Source: University of Alabama

Tailored 'activity coaching' by smartphone

Tailored activity monitoring. Credit: Image courtesy of University of Twente

Today's smartphone user can obtain a lot of data about his or her health, thanks to built-in or separate sensors. Researcher Harm op den Akker of the University of Twente (CTIT Institute) now takes this health monitoring to a higher level. Using the system he developed, the smartphone also acts as an 'activity coach': it advices the user to walk or take a rest. In what way the user wants to be addressed, is typically something the system learns by itself. Op den Akker conducted his research at Roessingh Research and Development in Enschede. October 17, he defends his PhD-thesis.

The new telemedicine system was tested for three months, among a group of COPD patients -- a chronic lung disease. For these patients, physical activity is very important but it can also lead to an oppressed feeling and thus, to over-cautiousness. Using the coaching system of Van den Akker, the patients carry a small movement sensor and a smartphone. The system calculates if it is advisable to take a rest or, on the other hand, have a walk. The system is 'context aware': it looks at the time of day, the weather, the surroundings of the patient and determines if the time is right for taking some exercise.

Tone of voice

In addition, the system knows how the patient wants to be addressed. Some people don't mind an imperative tone of voice 'go for a 10 minutes' walk', others prefer a more friendly advice: 'what if you would take a walk in the park?' Op den Akker designed learning algorithms for this: the system learns the preferences of the user by itself. Future versions of the system may not use text messages anymore, but an 'avatar' on the screen, enabling interaction with the user as well. For this, Op den Akker has started starting cooperation with the Human Media Interaction group of the University of Twente.

Roessingh Research & Development (RRD) is the research department of Roessingh rehabilitation centre in Enschede, The Netherlands. RRD closely cooperates with the University of Twente in many projects. Op den Akker conducted his research at RRD and UT's CTIT Institute, under supervision of Hermie Hermens, Professor in Neuromuscular Control and Telemedicine. A spin-off company of the university, Inertia Technology, developed the movement sensor used in this project.

Op den Akker's PhD-thesis is titled 'Smart tailoring of real-time physical activity coaching systems'.

Source: University of Twente

How does the brain react to virtual reality? Completely different pattern of activity in brain

Illusions (stock image). UCLA neurophysicists have found that space-mapping neurons in the brain react differently to virtual reality than they do to real-world environments. Credit: © agsandrew / Fotolia

UCLA neurophysicists have found that space-mapping neurons in the brain react differently to virtual reality than they do to real-world environments. Their findings could be significant for people who use virtual reality for gaming, military, commercial, scientific or other purposes.

"The pattern of activity in a brain region involved in spatial learning in the virtual world is completely different than when it processes activity in the real world," said Mayank Mehta, a UCLA professor of physics, neurology and neurobiology in the UCLA College and the study's senior author. "Since so many people are using virtual reality, it is important to understand why there are such big differences."

The study was published today in the journal Nature Neuroscience.

The scientists were studying the hippocampus, a region of the brain involved in diseases such as Alzheimer's, stroke, depression, schizophrenia, epilepsy and post-traumatic stress disorder. The hippocampus also plays an important role in forming new memories and creating mental maps of space. For example, when a person explores a room, hippocampal neurons become selectively active, providing a "cognitive map" of the environment.

The mechanisms by which the brain makes those cognitive maps remains a mystery, but neuroscientists have surmised that the hippocampus computes distances between the subject and surrounding landmarks, such as buildings and mountains. But in a real maze, other cues, such as smells and sounds, can also help the brain determine spaces and distances.

To test whether the hippocampus could actually form spatial maps using only visual landmarks, Mehta's team devised a noninvasive virtual reality environment and studied how the hippocampal neurons in the brains of rats reacted in the virtual world without the ability to use smells and sounds as cues.

Researchers placed a small harness around rats and put them on a treadmill surrounded by a "virtual world" on large video screens -- a virtual environment they describe as even more immersive than IMAX -- in an otherwise dark, quiet room. The scientists measured the rats' behavior and the activity of hundreds of neurons in their hippocampi, said UCLA graduate student Lavanya Acharya, a lead author on the research.

The researchers also measured the rats' behavior and neural activity when they walked in a real room designed to look exactly like the virtual reality room.

The scientists were surprised to find that the results from the virtual and real environments were entirely different. In the virtual world, the rats' hippocampal neurons seemed to fire completely randomly, as if the neurons had no idea where the rat was -- even though the rats seemed to behave perfectly normally in the real and virtual worlds.

"The 'map' disappeared completely," said Mehta, director of a W.M. Keck Foundation Neurophysics center and a member of UCLA's Brain Research Institute. "Nobody expected this. The neuron activity was a random function of the rat's position in the virtual world."

Explained Zahra Aghajan, a UCLA graduate student and another of the study's lead authors: 

"In fact, careful mathematical analysis showed that neurons in the virtual world were calculating the amount of distance the rat had walked, regardless of where he was in the virtual space."

They also were shocked to find that although the rats' hippocampal neurons were highly active in the real-world environment, more than half of those neurons shut down in the virtual space.

The virtual world used in the study was very similar to virtual reality environments used by humans, and neurons in a rat's brain would be very hard to distinguish from neurons in the human brain, Mehta said.

His conclusion: "The neural pattern in virtual reality is substantially different from the activity pattern in the real world. We need to fully understand how virtual reality affects the brain."

Neurons Bach would appreciate

In addition to analyzing the activity of individual neurons, Mehta's team studied larger groups of the brain cells. Previous research, including studies by his group, have revealed that groups of neurons create a complex pattern using brain rhythms.

"These complex rhythms are crucial for learning and memory, but we can't hear or feel these rhythms in our brain. They are hidden under the hood from us," Mehta said. "The complex pattern they make defies human imagination. The neurons in this memory-making region talk to each other using two entirely different languages at the same time. One of those languages is based on rhythm; the other is based on intensity."

Every neuron in the hippocampus speaks the two languages simultaneously, Mehta said, comparing the phenomenon to the multiple concurrent melodies of a Bach fugue.

Mehta's group reports that in the virtual world, the language based on rhythm has a similar structure to that in the real world, even though it says something entirely different in the two worlds. The language based on intensity, however, is entirely disrupted.

When people walk or try to remember something, the activity in the hippocampus becomes very rhythmic and these complex, rhythmic patterns appear, Mehta said. Those rhythms facilitate the formation of memories and our ability to recall them. Mehta hypothesizes that in some people with learning and memory disorders, these rhythms are impaired.

"Neurons involved in memory interact with other parts of the hippocampus like an orchestra," Mehta said. "It's not enough for every violinist and every trumpet player to play their music flawlessly. They also have to be perfectly synchronized."

Mehta believes that by retuning and synchronizing these rhythms, doctors will be able to repair damaged memory, but said doing so remains a huge challenge.

"The need to repair memories is enormous," noted Mehta, who said neurons and synapses -- the connections between neurons -- are amazingly complex machines.

Previous research by Mehta showed that the hippocampal circuit rapidly evolves with learning and that brain rhythms are crucial for this process. Mehta conducts his research with rats because analyzing complex brain circuits and neural activity with high precision currently is not possible in humans.

Other co-authors of the study were Jason Moore, a UCLA graduate student; Cliff Vuong, a research assistant who conducted the research as a UCLA undergraduate; and UCLA postdoctoral scholar Jesse Cushman. The research was funded by the W.M. Keck Foundation and the National Institutes of Health.

Source: University of California - Los Angeles

That smartphone is giving your thumbs superpowers

While neuroscientists have long studied brain plasticity in expert groups--musicians or video gamers, for instance--smartphones present an opportunity to understand how regular life shapes the brains of regular people. Credit: © Antonioguillem / Fotolia

When people spend time interacting with their smartphones via touchscreen, it actually changes the way their thumbs and brains work together, according to a report in the Cell Press journal Current Biology on December 23. More touchscreen use in the recent past translates directly into greater brain activity when the thumbs and other fingertips are touched, the study shows.

"I was really surprised by the scale of the changes introduced by the use of smartphones," says Arko Ghosh of the University of Zurich and ETH Zurich in Switzerland. "I was also struck by how much of the inter-individual variations in the fingertip-associated brain signals could be simply explained by evaluating the smartphone logs."

It all started when Ghosh and his colleagues realized that our newfound obsession with smartphones could be a grand opportunity to explore the everyday plasticity of the human brain. Not only are people suddenly using their fingertips, and especially their thumbs, in a new way, but many of us are also doing it an awful lot, day after day. Not only that, but our phones are also keeping track of our digital histories to provide a readymade source of data on those behaviors.

Ghosh explains it this way: "I think first we must appreciate how common personal digital devices are and how densely people use them. What this means for us neuroscientists is that the digital history we carry in our pockets has an enormous amount of information on how we use our fingertips (and more)."

While neuroscientists have long studied brain plasticity in expert groups--musicians or video gamers, for instance--smartphones present an opportunity to understand how regular life shapes the brains of regular people.

To link digital footprints to brain activity in the new study, Ghosh and his team used electroencephalography (EEG) to record the brain response to mechanical touch on the thumb, index, and middle fingertips of touchscreen phone users in comparison to people who still haven't given up their old-school mobile phones.

The researchers found that the electrical activity in the brains of smartphone users was 

enhanced when all three fingertips were touched. In fact, the amount of activity in the cortex of the brain associated with the thumb and index fingertips was directly proportional to the intensity of phone use, as quantified by built-in battery logs. The thumb tip was even sensitive to day-to-day fluctuations: the shorter the time elapsed from an episode of intense phone use, the researchers report, the larger was the cortical potential associated with it.

The results suggest to the researchers that repetitive movements over the smooth touchscreen surface reshape sensory processing from the hand, with daily updates in the brain's representation of the fingertips. And that leads to a pretty remarkable idea: "We propose that cortical sensory processing in the contemporary brain is continuously shaped by personal digital technology," Ghosh and his colleagues write.

What exactly this influence of digital technology means for us in other areas of our lives is a question for another day. The news might not be so good, Ghosh and colleagues say, noting evidence linking excessive phone use with motor dysfunctions and pain.

Source: Cell Press

Thumbs-up for mind-controlled robotic arm

This is an image showing one of four new hand movements from the 10D control of the robotic arm. Credit: Journal of Neural Engineering/IOP Publishing

A paralysed woman who controlled a robotic arm using just her thoughts has taken another step towards restoring her natural movements by controlling the arm with a range of complex hand movements.

Thanks to researchers at the University of Pittsburgh, Jan Scheuermann, who has longstanding quadriplegia and has been taking part in the study for over two years, has gone from giving "high fives" to the "thumbs-up" after increasing the manoeuvrability of the robotic arm from seven dimensions (7D) to 10 dimensions (10D).

The extra dimensions come from four hand movements--finger abduction, a scoop, thumb extension and a pinch--and have enabled Jan to pick up, grasp and move a range of objects much more precisely than with the previous 7D control.

It is hoped that these latest results, which have been published today, 17 December, in IOP Publishing's Journal of Neural Engineering, can build on previous demonstrations and eventually allow robotic arms to restore natural arm and hand movements in people with upper limb paralysis.

Jan Scheuermann, 55, from Pittsburgh, PA had been paralysed from the neck down since 2003 due to a neurodegenerative condition. After her eligibility for a research study was confirmed in 2012, Jan underwent surgery to be fitted with two quarter-inch electrode grids, each fitted with 96 tiny contact points, in the regions of Jan's brain that were responsible for right arm and hand movements.

After the electrode grids in Jan's brain were connected to a computer, creating a brain-machine interface (BMI), the 96 individual contact points picked up pulses of electricity that were fired between the neurons in Jan's brain.

Computer algorithms were used to decode these firing signals and identify the patterns associated with a particular arm movement, such as raising the arm or turning the wrist.

By simply thinking of controlling her arm movements, Jan was then able to make the robotic arm reach out to objects, as well as move it in a number of directions and flex and rotate the wrist. It also enabled Jan to "high five" the researchers and feed herself dark chocolate.

Two years on from the initial results, the researchers at the University of Pittsburgh have now shown that Jan can successfully manoeuvre the robotic arm in a further four dimensions through a number of hand movements, allowing for more detailed interaction with objects.

The researchers used a virtual reality computer program to calibrate Jan's control over the robotic arm, and discovered that it is crucial to include virtual objects in this training period in order to allow reliable, real-time interaction with objects.

Co-author of the study Dr Jennifer Collinger said: "10D control allowed Jan to interact with objects in different ways, just as people use their hands to pick up objects depending on their shapes and what they intend to do with them. We hope to repeat this level of control with additional participants and to make the system more robust, so that people who might benefit from it will one day be able to use brain-machine interfaces in daily life.

"We also plan to study whether the incorporation of sensory feedback, such as the touch and feel of an object, can improve neuroprosthetic control."

Commenting on the latest results, Jan Scheuermann said: ""This has been a fantastic, thrilling, wild ride, and I am so glad I've done this."

"This study has enriched my life, given me new friends and co-workers, helped me contribute to research and taken my breath away. For the rest of my life, I will thank God every day for getting to be part of this team."

Source: Institute of Physics

Advanced biological computer developed

Microprocessor with DNA (illustration). Scientists have developed and constructed an advanced biological transducer, a computing machine capable of manipulating genetic codes, and using the output as new input for subsequent computations Credit: © Giovanni Cancemi / Fotolia

Using only biomolecules (such as DNA and enzymes), scientists at the Technion-Israel Institute of Technology have developed and constructed an advanced biological transducer, a computing machine capable of manipulating genetic codes, and using the output as new input for subsequent computations. The breakthrough might someday create new possibilities in biotechnology, including individual gene therapy and cloning.

The findings appear today (May 23, 2013) in Chemistry & Biology (Cell Press).
Interest in such biomolecular computing devices is strong, mainly because of their ability (unlike electronic computers) to interact directly with biological systems and even living organisms. No interface is required since all components of molecular computers, including hardware, software, input and output, are molecules that interact in solution along a cascade of programmable chemical events.

"Our results show a novel, synthetic designed computing machine that computes iteratively and produces biologically relevant results," says lead researcher Prof. Ehud Keinan of the Technion Schulich Faculty of Chemistry. "In addition to enhanced computation power, this DNA-based transducer offers multiple benefits, including the ability to read and transform genetic information, miniaturization to the molecular scale, and the aptitude to produce computational results that interact directly with living organisms."

The transducer could be used on genetic material to evaluate and detect specific sequences, and to alter and algorithmically process genetic code. Similar devices, says Prof. Keinan, could be applied for other computational problems.

"All biological systems, and even entire living organisms, are natural molecular computers. Every one of us is a biomolecular computer, that is, a machine in which all components are molecules "talking" to one another in a logical manner. The hardware and software are complex biological molecules that activate one another to carry out some predetermined chemical tasks. The input is a molecule that undergoes specific, programmed changes, following a specific set of rules (software) and the output of this chemical computation process is another well defined molecule."

Also contributing to the research were postdoctoral fellows Dr. Tamar Ratner and Dr. Ron Piran of the Technion's Schulich Faculty of Chemistry, and Dr. Natasha Jonoska of the Department of Mathematics at the University of South Florida.

Source:  American Technion Society