Simple Innovation to Electrodes Makes a Big Difference

The electroencephalogram (EEG) for human uses has been around since 1924. Small metal discs placed along the scalp measure electrical activity in the human brain, important in diagnosing or evaluating epilepsy, sleep disorders and other conditions.

But these electrodes have changed little since their introduction, and are far from perfect. Among other things, they pick up extraneous noise and movement in addition to brain wave activity, often making the readings difficult to interpret.

Walt Besio thinks he has a better way.

The National Science Foundation-funded scientist, who is associate professor of biomedical engineering at the University of Rhode Island, has invented a new and improved electrode, one that produces a performance difference that he says is akin to “taking the rabbit ears you used to have for your television set, and converting to high definition.”

His innovation is relatively simple, but apparently makes a big difference. Besio added two new metal rings around the basic disc, a change that eliminates outside noises and improves spatial resolution.

"EEG has two main problems: It’s very noisy and contaminated with artifacts, and it’s spatial resolution is bad," he explains. "We have improved the signal-to-noise ratio. It’s four times better than it was before. Because it is now a very local signal, it means we can put electrodes closer together, which improves spatial resolution, meaning you can better determine where the signal is coming from."

The additional rings work almost like an inner tube tossed on top of a rippling body of water. “The water is flat in the center of the inner tube and choppy on the outside,” he says. “The outer rings on the electrodes behave like that inner tube.”

For researchers and clinicians, having improved electrodes could open up potential new uses, as well as improve current ones-more accurate epilepsy diagnosis, for example, as well as the promise of “reading” someone’s thoughts in the future, with the goal, for example, of activating an otherwise inert body part, such as an arm or leg, and ultimately helping people with spinal cord injuries.

The aim is to have the highly sensitive electrodes first translate a person’s thoughts into electrical impulses that can be read by a computer, then, eventually move to robots, and later, limbs. Other scientists are conducting similar research, but Besio wants to show “that it works better with these types of electrodes.”

A Confederacy of Senses

Research on multisensory speech perception in recent years has helped revolutionize our understanding of how the brain organizes the information it receives from our many different senses, UC Riverside psychology professor Lawrence D. Rosenblum writes in the January 2013 issue of Scientific American.

“Neuroscientists and psychologists have largely abandoned early ideas of the brain as a Swiss Army knife, in which many distinct regions are dedicated to different senses,” he says. “Instead scientists now think that the brain has evolved to encourage as much cross talk as possible between the senses — that the brain’s sensory regions are physically intertwined.”

The article, “A Confederacy of Senses,” explains how research in the past 15 years has demonstrated that no sense works alone. An abstract of the article can be read here.

“The multisensory revolution is also suggesting new ways to improve devices for the blind and deaf, such as cochlear implants,” Rosenblum writes. This research also has improved speech-recognition software, he says.

Researchers have discovered that the brain “does not channel visual information from the eyes into one neural container and auditory information from the ears into another, discrete, container as though it were sorting coins,” Rosenblum writes. “Rather our brains derive meaning from the world in as many ways as possible by blending the diverse forms of sensory perception.”

Rosenblum is the author of “See What I’m Saying: The Extraordinary Powers of Our Five Senses” (Norton, 2010), and has spent two decades studying multisensory perception, lipreading and hearing. His research has been supported by the National Science Foundation and the National Institutes of Health. He is known internationally for his research on risks the inaudibility of hybrid cars pose for blind and other pedestrians.

Help for when noses no longer smell properly

A psychological test, available for the first time, is intended to make the counselling and treatment of patients with olfactory dysfunction significantly easier. The new method has been developed by the University Department of Neurology at the MedUni Vienna.

The new investigation method provides the first easy-to-use testing process that measures subjective impairments caused by problems with the sense of smell. The test also examines how the impairment impacts on the patient’s quality of life. The aim of the test is to make targeted treatment and counselling to sufferers significantly easier in the future.

According to Gisela Pusswald, the developer of the test who works in the University Department of Neurology, patients often complain that their food no longer tastes like it used to and that they are unable to perceive perfumes or body odour at all, or only to a limited extent. The associated uncertainty of everyday living is often an even greater challenge. Says Pusswald: “Many patients are afraid that they will be unable to smell a gas leak if one occurs. The same goes for smoke, since they are unable to detect its smell.”

Worldwide, one in five people are affected by olfactory disturbances. The head of the test’s development, Johann Lehrner from the University Department of Neurology, explains why these conditions are extremely serious: “The debilitation of people with olfactory disturbances can be quite significant and can even cause persistent depressive states.” According to Lehrner, it is a worldwide phenomenon: “International studies estimate that one in five people worldwide aged between 20 and 90 have a disturbed sense of smell.”

English version of the test currently in development
The test, which has had its première in Vienna, was developed for the entire German-speaking region. Clinicians therefore now, for the first time, have a method that they can use and evaluate easily and one that delivers fast results. It gives experts the ability to very quickly obtain a good estimate of the extent of the problem. The German version of the test is currently being adapted for the English-speaking world.

Mild brain cooling after head injury prevents epileptic seizures in lab study

Mild cooling of the brain after a head injury prevents the later development of epileptic seizures, according to an animal study reported this month in the Annals of Neurology.

Epilepsy can result from genetics or brain damage. Traumatic head injury is the leading cause of acquired epilepsy in young adults. It is often difficult to manage with antiepileptic drugs. The mechanisms  behind the onset of epileptic seizures after brain injury are not known . There is currently no treatment to cure it, prevent it, or even limit its severity.

The multi-institutional research team used a rodent model of acquired epilepsy in which animals develop chronic spontaneous recurrent seizures -the hallmark of epilepsy- after a contusive head injury similar to that causing epilepsy in humans. The rats were randomized to either mock-cooling or cooling of the contused brain by no more than 2 Celsius degrees. This degree of cooling, the authors explained, is known to be safe and to decrease mortality of patients with head injury.  The rats  were then monitored for four months after injury and epilepsy was evaluated by intracranial EEG. The contused brain was cooled continuously with special headsets engineered to passively dissipate heat. No Peltier cells or other power sources for refrigeration were needed.

The investigators report that cooling by just 2 degrees celsius for 5 weeks beginning 3 days after injury virtually abolished the later development of epileptic seizure activity. This effect persisted through the end of the study. The treatment induced no additional pathology or inflammation, and restored neuronal activity depressed by the injury.

“These findings demonstrate for the first time that prevention of epileptic seizures after traumatic brain brain injury is possible, and that epilepsy prophylaxis in patients could be achieved more easily than previously thought, said  the lead author of the study,  Raimondo D’Ambrosio, UW associate professor of neurological surgery.  He added that a clinical trial is required to verify the findings in head injury patients.

Re-tuning responses in the visual cortex

New research led by Shigeru Tanaka of the University of Electro-Communications and visiting scientist at the RIKEN Brain Science Institute has shown that the responses of cells in the visual cortex can be ‘re-tuned’ by experience.

Experiments on kittens in the 1960s showed that the primary visual cortex contains neurons that fire selectively to straight lines of specific orientations. These cells are organized into alternating columns that receive inputs from the left or right eye. The kitten experiments also showed that proper brain development is highly dependent on sensory information. Closing one eye altered the organization of the columns, so that those that should have received inputs from the closed eye were reduced in width, whereas those that received inputs from the open eye were much wider than normal.

The normal columnar organization can be restored if the closed eye is re-opened within a critical period of brain development. The effect of sensory experience on the orientation selectivity of neurons in the primary visual cortex is, however, unknown.

To investigate, Tanaka and his colleagues reared mice and fitted them with specially designed goggles through which they can only perceive vertically oriented visual stimuli, for a one-week period, between 3 and 15 weeks of age. Immediately after removing the goggles, they created a ‘window’ in the skull bone lying over the visual cortex to examine the cell response under the microscope.

Rearing the mice in this way had a significant effect on the properties of neurons in the primary visual cortex. The researchers found that the number of cells responding to vertical orientation increased, while the number responding to other orientation decreased. They also found that the extent of these changes depended on the age at which they fitted the animals with the goggles. Mice fitted with the goggles between 4 and 7 weeks of age had more cells that were sensitive to the experienced (vertical) orientation than those fitted later.

These findings show that there is a critical period of plasticity between 4 and 7 weeks, during which cells in the primary visual cortex are particularly sensitive to sensory experience and that plasticity persists in older animals, albeit to a lesser extent. They also suggest that plasticity in younger and older animals involves different mechanisms.

“When we put similar goggles on kittens, the age at which we started goggle rearing determined the reversibility of orientation selectivity,” says Tanaka. “We would now like to clarify the differences and commonalities of the mechanisms in cats and mice.”

A new type of nerve cell found in the brain

Scientists at Karolinska Institutet in Sweden, in collaboration with colleagues in Germany and the Netherlands, have identified a previously unknown group of nerve cells in the brain. The nerve cells regulate cardiovascular functions such as heart rhythm and blood pressure. It is hoped that the discovery, which is published in the Journal of Clinical Investigation, will be significant in the long term in the treatment of cardiovascular diseases in humans.

The scientists have managed to identify in mice a previously totally unknown group of nerve cells in the brain. These nerve cells, also known as ‘neurons’, develop in the brain with the aid of thyroid hormone, which is produced in the thyroid gland. Patients in whom the function of the thyroid gland is disturbed and who therefore produce too much or too little thyroid hormone, thus risk developing problems with these nerve cells. This in turn has an effect on the function of the heart, leading to cardiovascular disease.

It is well-known that patients with untreated hyperthyroidism (too high a production of thyroid hormone) or hypothyroidism (too low a production of thyroid hormone) often develop heart problems. It has previously been believed that this was solely a result of the hormone affecting the heart directly. The new study, however, shows that thyroid hormone also affects the heart indirectly, through the newly discovered neurons.

"This discovery opens the possibility of a completely new way of combating cardiovascular disease", says Jens Mittag, group leader at the Department of Cell and Molecular Biology at Karolinska Institutet. "If we learn how to control these neurons, we will be able to treat certain cardiovascular problems like hypertension through the brain. This is, however, still far in the future. A more immediate conclusion is that it is of utmost importance to identify and treat pregnant women with hypothyroidism, since their low level of thyroid hormone may harm the production of these neurons in the foetus, and this may in the long run cause cardiovascular disorders in the offspring."

Removing protein ‘garbage’ in nerve cells may help control 2 neurodegenerative diseases

Neuroscientists at Georgetown University Medical Center say they have new evidence that challenges scientific dogma involving two fatal neurodegenerative diseases — amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) — and, in the process, have uncovered a possible therapeutic target as a novel strategy to treat both disorders.

The study, posted online in the Journal of Biological Chemistry, found that the issue in both diseases is the inability of the cell’s protein garbage disposal system to “pull out” and destroy TDP-43, a powerful, sometimes mutated gene that produces excess amounts of protein inside the nucleus of a nerve cell, or neuron.

"This finding suggests that if we’re able to ‘rev up’ that clearance machinery and help the cell get rid of the bad actors, it could possibly reduce or slow the development of ALS and FTD," says the study’s lead investigator, neuroscientist Charbel E-H Moussa, MB, PhD. "The potential of such an advance is very exciting." He cautions, though, that determining if this strategy is possible in humans could take many years and will involve teams of researchers.

The way to rev up protein disposal is to add parkin — the cell’s natural disposal units — to brain cells. In this study, Moussa and his colleagues demonstrated in two animal experiments that delivering parkin genes to neurons slowed down ALS pathologies linked to TDP-43.”

Moussa says that his study further demonstrates that clumps known as “inclusions” of TDP-43 protein found inside neuron bodies in both disorders do not promote these diseases, as some researchers have argued.

What happens in both diseases is that this protein, which is a potent regulator of thousands of genes, leaves the nucleus and collects inside the gel-like cytoplasm of the neuron. In ALS, also known as Lou Gehrig’s disease, this occurs in motor neurons, affecting movement; in FTD, it occurs in the frontal lobe of the brain, leading to dementia.

"In both diseases, TDP-43 is over-expressed or mutated, and the scientific debate has been whether loss of TDP-43 in the nucleus or gain of TDP-43 in the cytoplasm is the problem," Moussa says.

"Our study suggests TDP-43 in the cell cytoplasm is deposited there in order to eventually be destroyed — without contributing to disease — and that TDP-43 in the nucleus is causing the damage," he says. "Because so much protein is being produced, the cell can’t keep up with removing these toxic particles in the nucleus and the dumping of them in the cytoplasm. There may be a way to fix this problem."

Moussa has long studied parkin, a molecule best known, when mutated and inactive, for its role in a familial form of Parkinson’s disease. He has studied it in Alzheimer’s disease and other forms of dementia. His hypothesis, which he has demonstrated in several recently published studies, is that parkin could help remove the toxic fragments of amyloid beta protein that builds up in the brains of Alzheimer’s disease patients.

What’s more, he developed a method to clear this amyloid beta when it begins to build up in neurons — a gene therapy strategy he has shown works in rodents. Work continues on this potential therapy.

In this study, Moussa found that parkin “tags” TDP-43 protein in the nucleus with a molecule that takes it from the nucleus and into the cytoplasm of the cell. “This is good. If TDP-43 is in the cytoplasm, it will prevent further nuclear damage and deregulation of genetic materials that determine protein identity,” he says.

"This discovery challenges the dogma that accumulation of TDP-43 in the cytoplasm is," Moussa says. "We think parkin is tagging proteins in the nucleus for destruction, but there just isn’t enough parkin around — compared with over-production of TDP-43 — to do the job."

Moussa says his next research steps will be to inject a drug that activates parkin to see whether that can prolong the lifespan and reduce motor defects in mice with ALS.

(Image: iStock)

Brain imaging insight into cannabis as a pain killer

The pain relief offered by cannabis varies greatly between individuals, a brain imaging study carried out at the University of Oxford suggests.

The researchers found that an oral tablet of THC, the psychoactive ingredient in cannabis, tended to make the experience of pain more bearable, rather than actually reduce the intensity of the pain.

MRI brain imaging showed reduced activity in key areas of the brain that substantiated the pain relief the study participants experienced. 

'We have revealed new information about the neural basis of cannabis-induced pain relief,' says lead researcher Dr Michael Lee of Oxford University's Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB). 

'Cannabis does not seem to act like a conventional pain medicine. Some people respond really well, others not at all, or even poorly,' he says. 'Brain imaging shows little reduction in the brain regions that code for the sensation of pain, which is what we tend to see with drugs like opiates. Instead cannabis appears to mainly affect the emotional reaction to pain in a highly variable way.'

Long-term pain, often without clear cause, is a complex healthcare problem. Different approaches are often needed to help patient manage pain, and can include medications, physiotherapy and other forms of physical therapy, and psychological support. 

For a few patients, cannabis or cannabis-based medications remain effective when other drugs have failed to control pain, while others report very little effect of the drug on their pain but experience side-effects.

'We know little about cannabis and what aspects of pain it affects, or which people might see benefits over the side-effects or potential harms in the long term. We carried out this study to try and get at what is happening when someone experiences pain relief using cannabis,' says Dr Lee.

He adds: ‘Our small-scale study, in a controlled setting, involved 12 healthy men and only one of many compounds that can be derived from cannabis. That’s quite different from doing a study with patients.

'My view is the findings are of interest scientifically but it remains to see how they impact the debate about use of cannabis-based medicines. Understanding cannabis' effects on clinical outcomes, or the quality of life of those suffering chronic pain, would need research in patients over long time periods.'

(The paper ‘Amygdala activity contributes to the dissociative effect of cannabis on pain perception' by Michael C. Lee, Markus Ploner, Katja Wiech, Ulrike Bingel, Vishvarani Wanigasekera, Jonathan Brooks, David K. Menon, Irene Tracey (DOI: 10.1016/j.pain.2012.09.017) will appear in PAIN®, Volume 154, Issue 1 (January 2013) published by Elsevier)