Neuroscience

Scientists have shed light on how mechanisms in the brain work to give us a sense of location. Research at the University of Edinburgh tracked electrical signals in the part of the brain linked to spatial awareness.

Sense of where we are

The study could help us understand how, if we know a room, we can go into it with our eyes shut and find our way around. This is closely related to the way we map out how to get from one place to another.

Brain’s electrical activity

Scientists found that brain cells, which code location through increases in electrical activity, do not do so by talking directly to each other. Instead, they can only send each other signals through cells that are known to reduce electrical activity. This is unexpected as cells that reduce electrical signalling are often thought to simply supress brain activity.

Rhythms of brain activity

The research also looked at electrical rhythms or waves of brain activity. Previous studies have found that spatial awareness is linked to not only the number and strength of electrical signals but also where on the electrical wave they occur.

The research shows that the indirect communication between nerve cells that are involved in spatial awareness also helps to explain how these electrical waves are generated. This finding is surprising because its suggests that the same cellular mechanisms allow our brains to work out our location and generate rhythmic waves of activity.

Spatial awareness and the brain’s electrical rhythms are known to be affected in conditions such as schizophrenia and Alzheimer’s disease. The scientists work could therefore help research in these areas.

Research

The study, funded by the Biotechnology and Biological Research Council, is published in the journal Neuron.

It looked at connections between nerve cells in the brain needed for spatial awareness in mice and then used computer modelling to recreate patterns of neural activity found in the brain.

Rhythms in brain activity are very mysterious and the research helps shed some light on this area as well as helping us understand how our brains code spatial information. It is particularly interesting that cells thought to encode location do not signal to each other directly but do so through intermediary cells. This is somewhat like members of a team not talking to each other, but instead sending messages via members of an opposing side. -Matt Nolan (Centre for Integrative Physiology)

As we age, it just may be the ability to filter and eliminate old information – rather than take in the new stuff – that makes it harder to learn, scientists report.

“When you are young, your brain is able to strengthen certain connections and weaken certain connections to make new memories,” said Dr. Joe Z. Tsien, neuroscientist at the Medical College of Georgia at Georgia Regents University and Co-Director of the GRU Brain & Behavior Discovery Institute.

It’s that critical weakening that appears hampered in the older brain, according to a study in the journal Scientific Reports.

The NMDA receptor in the brain’s hippocampus is like a switch for regulating learning and memory, working through subunits called NR2A and NR2B. NR2B is expressed in higher percentages in children, enabling neurons to talk a fraction of a second longer; make stronger bonds, called synapses; and optimize learning and memory. This formation of strong bonds is called long-term potentiation. The ratio shifts after puberty, so there is more NR2A and slightly reduced communication time between neurons.

When Tsien and his colleagues genetically modified mice that mimic the adult ratio – more NR2A, less NR2B – they were surprised to find the rodents were still good at making strong connections and short-term memories but had an impaired ability to weaken existing connections, called long-term depression, and to make new long-term memories as a result. It’s called information sculpting and adult ratios of NMDA receptor subunits don’t appear to be very good at it.

“If you only make synapses stronger and never get rid of the noise or less useful information then it’s a problem,” said Tsien, the study’s corresponding author. While each neuron averages 3,000 synapses, the relentless onslaught of information and experiences necessitates some selective whittling. Insufficient sculpting, at least in their mouse, meant a reduced ability to remember things short-term – like the ticket number at a fast-food restaurant – and long-term – like remembering a favorite menu item at that restaurant.  Both are impacted in Alzheimer’s and age-related dementia.

All long-term depression was not lost in the mice, rather just response to the specific electrical stimulation levels that should induce weakening of the synapse. Tsien expected to find the opposite: that long-term potentiation was weak and so was the ability to learn and make new memories. “What is abnormal is the ability to weaken existing connectivity.”

Acknowledging the leap, this impaired ability could also help explain why adults can’t learn a new language without their old accent and why older people tend to be more stuck in their ways, the memory researcher said.

“We know we lose the ability to perfectly speak a foreign language if we learn than language after the onset of sexual maturity. I can learn English but my Chinese accent is very difficult to get rid of. The question is why,” Tsien said.

Tsien and his colleagues already have learned what happens when NR2B is overexpressed. He and East China Normal University researchers announced in 2009 the development of Hobbie-J, a smarter than average rat. A decade earlier, Tsien reported in the journal Nature the development of a smart mouse dubbed Doogie using the same techniques to over-express the NR2B gene in the hippocampus.

Doogie, Hobbie-J and their descendants have maintained superior memory as they age. Now Tsien is interested in following the NR2A over-expressing mouse to see what happens.

Scientists have long wondered how nerve cell activity in the brain’s hippocampus, the epicenter for learning and memory, is controlled — too much synaptic communication between neurons can trigger a seizure, and too little impairs information processing, promoting neurodegeneration. Researchers at Georgetown University Medical Center say they now have an answer. In the January 10 issue of Neuron, they report that synapses that link two different groups of nerve cells in the hippocampus serve as a kind of “volume control,” keeping neuronal activity throughout that region at a steady, optimal level.

"Think of these special synapses like the fingers of God and man touching in Michelangelo’s famous fresco in the Sistine Chapel," says the study’s senior investigator, Daniel Pak, PhD, an associate professor of pharmacology. "Now substitute the figures for two different groups of neurons that need to perform smoothly. The touching of the fingers, or synapses, controls activity levels of neurons within the hippocampus."

The hippocampus is a processing unit that receives input from the cortex and consolidates that information in terms of learning and memory. Neurons known as granule cells, located in the hippocampus’ dentate gyrus, receive transmissions from the cortex. Those granule cells then pass that information to the other set of neurons (those in the CA3 region of the hippocampus, in this study) via the synaptic fingers.

Those fingers dial up, or dial down, the volume of neurotransmission from the granule cells to the CA3 region to keep neurotransmission in the learning and memory areas of the hippocampus at an optimal flow — a concept known as homeostatic plasticity. “If granule cells try to transmit too much activity, we found, the synaptic junction tamps down the volume of transmission by weakening their connections, allowing the proper amount of information to travel to CA3 neurons,” says Pak. “If there is not enough activity being transmitted by the granule cells, the synapses become stronger, pumping up the volume to CA3 so that information flow remains constant.”

There are many such touching fingers in the hippocampus, connecting the so-called “mossy fibers” of the granule cells to neurons in the CA3 region. But importantly, not every one of the billions of neurons in the hippocampus needs to set its own level of transmission from one nerve cell to the other, says Pak.

To explain, he uses another analogy. “It had previously been thought that neurons act separately like cars, each working to keep their speed at a constant level even though signal traffic may be fast or slow. But we wondered how these neurons could process learning and memory information efficiently, while also regulating the speed by which they process and communicate that information.

"We believe, based on our study, that only the mossy fiber synapses on the CA3 neurons control the level of activity for the hippocampus — they are like the engine on a train that sets the speed for all the other cars, or neurons, attached to it," Pak says. "That frees up the other neurons to do the job they are tasked with doing — processing and encoding information in the forms of learning and memory."

Not only does the study offer a new model for how homeostatic plasticity in the hippocampus can co-exist with learning and memory, it also suggests a new therapeutic avenue to help patients with uncontrollable seizures, he says.

"The CA3 region is highly susceptible to seizures, so if we understand how homeostasis is maintained in these neurons, we could potentially manipulate the system. When there is an excessive level of CA3 neuronal activity in a patient, we could learn how to therapeutically turn it down."

It is said that classical music could make children more intelligent, but when you look at the scientific evidence, the picture is more mixed.

You have probably heard of the Mozart effect. It’s the idea that if children or even babies listen to music composed by Mozart they will become more intelligent. A quick internet search reveals plenty of products to assist you in the task. Whatever your age there are CDs and books to help you to harness the power of Mozart’s music, but when it comes to scientific evidence that it can make you more clever, the picture is more mixed. 

The phrase “the Mozart effect” was coined in 1991, but it is a study described two years later in the journal Nature that sparked real media and public interest about the idea that listening to classical music somehow improves the brain. It is one of those ideas that feels plausible. Mozart was undoubtedly a genius himself, his music is complex and there is a hope that if we listen to enough of it, a little of that intelligence might rub off on us.

The idea took off, with thousands of parents playing Mozart to their children, and in 1998 Zell Miller, the Governor of the state of Georgia in the US, even asked for money to be set aside in the state budget so that every newborn baby could be sent a CD of classical music. It’s not just babies and children who were deliberately exposed to Mozart’s melodies. When Sergio Della Sala, the psychologist and author of the book Mind Myths, visited a mozzarella farm in Italy, the farmer proudly explained that the buffalos were played Mozart three times a day to help them to produce better milk.

I’ll leave the debate on the impact on milk yield to farmers, but what about the evidence that listening to Mozart makes people more intelligent? Exactly what was it was that the authors of the initial study discovered that took public imagination by storm?

When you look back at the original paper, the first surprise is that the authors from the University of California, Irvine are modest in their claims and don’t even use the “Mozart effect” phrase in the paper. The second surprise is that it wasn’t conducted on children at all: it was in fact conducted with those stalwarts of psychological studies – young adult students. Only 36 students took part. On three occasions they were given a series of mental tasks to complete, and before each task, they listened either to ten minutes of silence, ten minutes of a tape of relaxation instructions, or ten minutes of Mozart’s sonata for two pianos in D major (K448).

The students who listened to Mozart did better at tasks where they had to create shapes in their minds. For a short time the students were better at spatial tasks where they had to look at folded up pieces of paper with cuts in them and to predict how they would appear when unfolded. But unfortunately, as the authors make clear at the time, this effect lasts for about fifteen minutes. So it’s hardly going to bring you a lifetime of enhanced intelligence.

Brain arousal

Nevertheless, people began to theorise about why it was that Mozart’s music in particular could have this effect. Did the complexity of music cause patterns of cortical firing in the brain similar to those associated with solving spatial puzzles?

More research followed, and a meta-analysis of sixteen different studies confirmed that listening to music does lead to a temporary improvement in the ability to manipulate shapes mentally, but the benefits are short-lived and it doesn’t make us more intelligent.

Then it began to emerge that perhaps Mozart wasn’t so special after all. In 2010 a larger meta-analysis of a greater number of studies again found a positive effect, but that other kinds of music worked just as well. One study found that listening to Schubert was just as good, and so was hearing a passage read out aloud from a Stephen King novel. But only if you enjoyed it. So, perhaps enjoyment and engagement are key, rather than the exact notes you hear.

Although we tend to associate the Mozart effect with babies and small children, most of these studies were conducted on adults, whose brains are of course at a very different stage of development. But in 2006 a large study was conducted in Britain involving eight thousand children. They listened either to ten minutes of Mozart’s String Quintet in D Major, a discussion about the experiment or to a sequence of three pop songs: Blur’s “Country House,” “Return of the Mack,” by Mark Morrison and PJ and Duncan’s “Stepping Stone”. Once again music improved the ability to predict paper shapes, but this time it wasn’t a Mozart effect, but a Blur effect. The children who listened to Mozart did well, but with pop music they did even better, so prior preference could come into it.

Whatever your musical choice, it seems that all you need to do a bit better at predictive origami is some cognitive arousal. Your mind needs to get a little more active, it needs something to get it going and that’s going to be whichever kind of music appeals to you. In fact, it doesn’t have to be music. Anything that makes you more alert should work just as well – doing a few star jumps or drinking some coffee, for instance.

There is a way in which music can make a difference to your IQ, though. Unfortunately it requires a bit more effort than putting on a CD. Learning to play a musical instrument can have a beneficial effect on your brain. Jessica Grahn, a cognitive scientist at Western University in London, Ontario says that a year of piano lessons, combined with regular practice can increase IQ by as much as three points.

So listening to Mozart won’t do you or your children any harm and could be the start of a life-long love of classical music. But unless you and your family have some urgent imaginary origami to do, the chances are that sticking on a sonata is not going to make you better at anything.

An experimental oral drug given to mice after a spinal cord injury was effective at improving limb movement after the injury, a new study shows.

The compound efficiently crossed the blood-brain barrier, did not increase pain and showed no toxic effects to the animals.

“This is a first to have a drug that can be taken orally to produce functional improvement with no toxicity in a rodent model,” said Sung Ok Yoon, associate professor of molecular & cellular biochemistry at Ohio State University and lead author of the study. “So far, in the spinal cord injury field with rodent models, effective treatments have included more than one therapy, often involving invasive means. Here, with a single agent, we were able to obtain functional improvement.”

The small molecule in this study was tested for its ability to prevent the death of cells called oligodendrocytes. These cells surround and protect axons, long projections of a nerve cell, by wrapping them in myelin. In addition to functioning as axon insulation, myelin allows for the rapid transmission of signals between nerve cells.

The drug preserved oligodendrocytes by inhibiting the activation of a protein called p75. Yoon’s lab previously discovered that p75 is linked to the death of these specialized cells after a spinal cord injury. When they die, axons that are supported by them degenerate.

“Because we know that oligodendrocytes continue to die for a long period of time after an injury, we took the approach that if we could put a brake on that cell death, we could prevent continued degeneration of axons,” she said. “Many researchers in the field are focusing on regeneration of neurons, but we specifically targeted a different type of cells because it allows a relatively long therapeutic window.”

An additional benefit of targeting oligodendrocytes is that it can amplify the therapeutic effect because a single oligodendrocyte myelinates multiple axons.

A current acute treatment for humans, methylprednisolone, must be administered within eight but not more than 24 hours after the injury to be effective at all. An estimated 1.3 million people in the United States are living with spinal cord injuries, experiencing paralysis and complications that include bladder, bowel and sexual dysfunction and chronic pain.

The experimental drug, called LM11A-31, was developed by study co-author Frank Longo, professor of neurology and neurological sciences at Stanford University. The drug is the first to be developed with a specific target, p75, as a potential therapy for spinal cord injury.

The research is published in the Jan. 9, 2013, issue of The Journal of Neuroscience.

Researchers gave three different oral doses of LM11A-31, as well as a placebo, to different groups of mice beginning four hours after injury and then twice daily for a 42-day experimental period. The scientists analyzed the compound’s effectiveness at improving limb movement and preventing myelin loss.

The spinal cord injuries in mice mimicked those caused in humans by the application of extensive force and pressure, resulting in loss of hind-limb and bladder function andexperimentally calibrated baseline difficulty in walking and swimming.

The researchers determined that the mice did not experience more pain than the placebo group at all the doses tested, suggesting that LM11A-31 does not worsen nerve pain after spinal cord injury.

Analysis showed that the extent of myelin sparing was dependent on the dose of the drug. Each dose – 10, 25 or 100 milligrams per kilogram of body weight – led to increasing myelin sparing, with the highest dose demonstrating the greatest effect.

The injury in the animals caused a loss of about 75 percent of myelinated axons in the lesion area in the placebo group. This loss was reduced so that myelinated axons reached more than half of the normal levels with LM11A-31 at 100 mg/kg. That was correlated with about a 50 percent increase in surviving oligodendrotcytes compared to those in the placebo group, Yoon said.

In behavior tests, only the highest dose of the compound led to improvements in motor function. Mice were tested in both weight-bearing and non-weight-bearing activities over the 42 days to evaluate their functional recovery.

Mice receiving the highest dose could walk with well-coordinated steps. In swimming tests, scientists saw similar improvements, with mice receiving the highest dose most able to coordinate hind-limb crisscross movement. The other treatment groups exhibited difficulty in walking and swimming.

Yoon said the findings may suggest that myelin sparing needs to reach a threshold of roughly 50 percent of normal levels before motor function improvements become measurable.

“The cellular analysis of the myelin profile detects small changes. Behavior is more complex, and we don’t think functional behavior necessarily improves in a linear fashion,” she said. “Still, these results clearly show that this is the first oral drug in spinal cord injury that works alone to improve function.”

University of Florida researchers and colleagues have identified a protein that, when absent, helps the body burn fat and prevents insulin resistance and obesity. The findings from the National Institutes of Health-funded study were published online ahead of print Sunday, Jan. 6, in the journal Nature Medicine.

The discovery could aid development of drugs that not only prevent obesity, but also spur weight loss in people who are already overweight, said Dr. Stephen Hsu, one of the study’s corresponding authors and a principal investigator with the UF Sid Martin Biotechnology Development Institute.

One-third of adults and about 17 percent of children in the United States are obese, according to the Centers for Disease Control and Prevention. Although unrelated studies have shown that lifestyle changes such as choosing healthy food over junk food and increasing exercise can help reduce obesity, people are often unable to maintain these changes over time, Hsu said.

“The problem is when these studies end and the people go off the protocols, they almost always return to old habits and end up eating the same processed foods they did before and gain back the weight they lost during the study,” he said. Developing drugs that target the protein, called TRIP-Br2, and mimic its absence may allow for the prevention of obesity without relying solely on lifestyle modifications, Hsu said.

First identified by Hsu, TRIP-Br2 helps regulate how fat is stored in and released from cells. To understand its role, the researchers compared mice that lacked the gene responsible for production of the protein, with normal mice that had the gene.

They quickly discovered that mice missing the TRIP-Br2 gene did not gain weight no matter what they ate — even when placed on a high-fat diet — and were otherwise normal and healthy. On the other hand, the mice that still made TRIP-Br2 gained weight and developed associated problems such as insulin resistance, type 2 diabetes and high cholesterol when placed on a high-fat diet. The normal and fat-resistant mice ate the same amount of food, ruling out differences in food intake as a reason why the mice lacking TRIP-Br2 were leaner.

“We had to explain why the animals eating so much fat were remaining lean and not getting high cholesterol. Where was this fat going?” Hsu said. “It turns out this protein is a master regulator. It coordinates expression of a lot of genes and controls the release of the fuel form of fat and how it is metabolized.”

When functioning normally, TRIP-Br2 restricts the amount of fat that cells burn as energy. But when TRIP-Br2 is absent, a fat-burning fury seems to occur in fat cells. Although other proteins have been linked to the storage and release of fat in cells, TRIP-Br2 is unique in that it regulates how cells burn fat in a few different ways, Hsu said. When TRIP-Br2 is absent, fat cells dramatically increase the release of free fatty acids and also burn fat to produce the molecular fuel called ATP that powers mitochondria — the cell’s energy source. In addition, cells free from the influence of TRIP-Br2 start using free fatty acids to generate thermal energy, which protects the body from exposure to cold.

“TRIP-Br2 is important for the accumulation of fat,” said Dr. Rohit N. Kulkarni, also a senior author of the paper and an associate professor of medicine at Harvard Medical School and the Joslin Diabetes Center. “When an animal lacks TRIP-Br2, it can’t accumulate fat.”

Because the studies were done mostly in mice, additional studies are still needed to see if the findings translate to humans.

“We are very optimistic about the translational promise of our findings because we showed that only human subjects who had the kind of fat (visceral) that becomes insulin-resistant also had high protein levels of TRIP-Br2,” Hsu said.

“Imagine you are able to develop drugs that pharmacologically mimic the complete absence of TRIP-Br2,” Hsu said. “If a patient started off fat, he or she would burn the weight off. If people are at risk of obesity and its associated conditions, such as type 2 diabetes, it would help keep them lean regardless of how much fat they ate. That is the ideal anti-obesity drug, one that prevents obesity and helps people burn off excess weight.”

Scientists have wrestled to understand why Huntington’s disease, which is caused by a single gene mutation, can produce such variable symptoms. An authoritative review by a group of leading experts summarizes the progress relating cell loss in the striatum and cerebral cortex to symptom profile in Huntington’s disease, suggesting a possible direction for developing targeted therapies. The article is published in the latest issue of the Journal of Huntington’s Disease.

Huntington’s disease (HD) is an inherited progressive neurological disorder for which there is presently no cure. It is caused by a dominant mutation in the HD gene leading to expression of mutant huntingtin (HTT) protein. Expression of mutant HTT causes subtle changes in cellular functions, which ultimately results in jerking, uncontrollable movements, progressive psychiatric difficulties, and loss of mental abilities.

Although it is caused by a single gene, there are major variations in the symptoms of HD. The pattern of symptoms shown by each individual during the course of the disease can differ considerably and present as varying degrees of movement disturbances, cognitive decline, and mood and behavioral changes. Disease duration is typically between ten and twenty years.

Recent investigations have focused on what the presence of the defective gene does to various structures in the brain and understanding the relationship between changes in the brain and the variability in symptom profiles in Huntington’s disease.

Analyses of post-mortem human HD tissue suggest that the variation in clinical symptoms in HD is strongly associated with the variable pattern of neurodegeneration in two major regions of the brain, the striatum and the cerebral cortex. The neurodegeneration of the striatum generally follows an ordered and topographical distribution, but comparison of post-mortem human HD tissue and in vivo neuroimaging techniques reveal that the disease produces a striking bilateral atrophy of the striatum, which in these recent studies has been found to be highly variable.

“What is especially interesting is that recent findings suggest that the pattern of striatal cell death shows regional differences between cases in the functionally and neurochemically distinct striosomal and matrix compartments of the striatum which correspond with symptom variation,” says author Richard L.M. Faull, MB, ChB, PhD, DSc, Director of the Centre for Brain Research, University of Auckland, New Zealand.

“Our own recent detailed quantitative study using stereological cell counting in the post-mortem human HD cortex has complemented and expanded the neuroimaging studies by providing a cortical cellular basis of symptom heterogeneity in HD,” continues Dr Faull. “In particular, HD cases which were dominated by motor dysfunction showed a major total cell loss (28% loss) in the primary motor cortex but no cell loss in the limbic cingulate cortex, whereas cases where mood symptoms predominated showed a total of 54% neuronal loss in the limbic cingulate cortex but no cell loss in the motor cortex. This suggests that the variable neuronal loss and alterations in the circuitry of the primary motor cortex and anterior cingulate cortex associated with the variable compartmental pattern of cell degeneration in the striatum contribute to the differential impairments of motor and mood functions in HD.”

The authors note that there are still questions to be answered in the field of HD pathology, such as, how and when pathological neuronal loss occurs; whether the progressive loss of neurons in the striatum is the primary process or is consequential to cortical cell dysfunction; and how these changes relate to symptom profiles.

“What is clear however is that the diverse symptoms of HD patients appear to relate to the heterogeneity of cell loss in both the striatum and cerebral cortex,” the authors conclude. “While there is currently no cure, this contemporary evidence suggests that possible genetic therapies aimed at HD gene silencing should be directed towards intervention at both the cerebral cortex and the striatum in the human brain. This poses challenging problems requiring the application of gene silencing therapies to quite widespread regions of the forebrain which may be assisted via CSF delivery systems using gene suppression agents that cross the CSF/brain barrier.”

New research reveals a shared genetic susceptibility to epilepsy and migraine. Findings published in Epilepsia (DOI: 10.1111/epi.12072), a journal of the International League Against Epilepsy (ILAE), indicate that having a strong family history of seizure disorders increases the chance of having migraine with aura (MA).

Medical evidence has established that migraine and epilepsy often co-occur in patients; this co-occurrence is called “comorbidity.” Previous studies have found that people with epilepsy are substantially more likely than the general population to have migraine headache. However, it is not clear whether that comorbidity results from a shared genetic cause.

"Epilepsy and migraine are each individually influenced by genetic factors," explains lead author Dr. Melodie Winawer from Columbia University Medical Center in New York. "Our study is the first to confirm a shared genetic susceptibility to epilepsy and migraine in a large population of patients with common forms of epilepsy."

For the present study, Dr. Winawer and colleagues analyzed data collected from participants in the Epilepsy Phenome/Genome Project (EPGP)—a genetic study of epilepsy patients and families from 27 clinical centers in the U.S., Canada, Argentina, Australia, and New Zealand. The study examined one aspect of EPGP: sibling and parent-child pairs with focal epilepsy or generalized epilepsy of unknown cause. Most people with epilepsy have no family members affected with epilepsy. EPGP was designed to look at those rare families with more than one individual with epilepsy, in order to increase the chance of finding genetic causes of epilepsy.

Analysis of 730 participants with epilepsy from 501 families demonstrated that the prevalence of MA—when additional symptoms, such as blind spots or flashing lights, occur prior to the headache pain— was substantially increased when there were several individuals in the family with seizure disorders. EPGP study participants with epilepsy who had three or more additional close relatives with a seizure disorder were more than twice as likely to experience MA than patients from families with fewer individuals with seizures. In other words, the stronger the genetic effect on epilepsy in the family, the higher the rates of MA. This result provides evidence that a gene or genes exist that cause both epilepsy and migraine.

Identification of genetic contributions to the comorbidity of epilepsy with other disorders, like migraine, has implications for epilepsy patients. Prior research has shown that coexisting conditions impact the quality of life, treatment success, and mortality of epilepsy patients, with some experts suggesting that these comorbidities may have a greater impact on patients than the seizures themselves. In fact, comorbid conditions are emphasized in the National Institutes of Health Epilepsy Research Benchmarks and in a recent report on epilepsy from the Institute of Medicine.

"Our study demonstrates a strong genetic basis for migraine and epilepsy, because the rate of migraine is increased only in people who have close (rather than distant) relatives with epilepsy and only when three or more family members are affected," concludes Dr. Winawer. "Further investigation of the genetics of groups of comorbid disorders and epilepsy will help to improve the diagnosis and treatment of these comorbidities, and enhance the quality of life for those with epilepsy."

Scientists have developed a quick, easy and cheap vision test to find out which part – and how much – of the brain of a stroke victim has been damaged, potentially enabling them to save more lives.

The test requires patients to look into a device for about ten minutes, enabling it to be used in the early stages of a stroke – even if the patient cannot move their limbs or speak.

This can help doctors diagnose and treat the stroke quickly and accurately, which is vital, as early treatment can greatly improve a person’s chances of survival and recovery, say Dr Corinne Carle and Professor Ted Maddess from The Vision Centre and The Australian National University.

According to the World Health Organisation, stroke is currently the world’s sixth commonest cause of death, accounting for 4.9% of all fatalities. In Australia it kills about 9000 people a year and hospitalises 35,000.

“Our new test automatically tracks the response of the patient’s eye pupils to different colours, and can show doctors whether the injury is located in the evolutionarily ‘new brain’ or the ‘old brain’,” Dr Carle says.

“The distinction is important because the ‘old brain’, or midbrain, controls things like the heart rate and blood pressure of the body. So if you find that the midbrain has been damaged, you’ll need to treat the patient much more aggressively, because there’s a higher risk of death.”

On the other hand, an injury in the ‘new brain’ – the cortex – may cause permanent blindness in a part of the person’s visual field, or difficulty in their thoughts, speech and movement, but has a lower risk of death, she says.

Using the TrueField Analyzer, a device developed by Prof. Maddess’ Vision Centre team and the Australian company Seeing Machines, the researchers tested how the pupils respond to images on LCD screens. A mixture of red, green and yellow coloured stimuli were provided to each eye, at 24 locations in the person’s visual field.

Two video cameras using infrared lighting recorded the instant response of the pupils, which was then analysed by a computer.

The colours red, green and yellow were chosen because they are processed by different parts of the brain, Dr Carle explains. In mammals, the cortex, or ‘new brain’, is the most recently evolved area, and allows humans to differentiate between red and green.

The ‘ancient’ midbrain, on the other hand, is red-green colourblind, but can detect the colour yellow.

“If the pupils don’t react when red changes to green, we know that the damage is in the cortex. The same concept applies to the yellow stimulus,” says Dr Carle. “The test has been successful in checking the vision of people with glaucoma or type-1 diabetes, and we have now tweaked the stimuli for stroke patients as well.”

Prof. Ted Maddess says that the test will complement various types of brain scans.

“A CT scan tells you where the bleed is, but it doesn’t show you everything,” he says. “For instance, the blood could have cleared up in a particular part of the brain during the scan, or where swelling has reduced the function of a nearby part that looks fine on the scan. It may also miss injuries that are too small, or those that occur in the midbrain, where it doesn’t scan well.”

This is where the test can be useful, Prof. Maddess says. As every single vision cell is wired into a different part of the brain, by testing a particular area in the visual field, doctors can check if the corresponding part of the brain is functioning or not.

The test can be used to monitor stroke patients’ recovery, Prof. Maddess says: “Currently, apart from brain scans, there is no cheap, routine test that can quantify the amount of improvement that results from a treatment. Stroke patients have a very high risk of recurrence, so it’s important that doctors can accurately assess their recovery.”

“The TrueField Analyzer is small, affordable and the test only takes ten minutes,” he says. Working together with neurologists, the research team will start clinical tests with stroke patients in February this year.

The team’s study “The pupillary response to color and luminance variant multifocal stimuli” by Corinne F. Carle, Andrew C. James and Ted Maddess is published in the latest issue of Investigative Ophthalmology & Visual Science (IOVS).

The production of new neurons in the adult normal cortex in response to the antidepressant, fluoxetine, is reported in a study published online this week in Neuropsychopharmacology.

The research team, which is based at the Institute for Comprehensive Medical Science, Fujita Health University, Aichi, has previously demonstrated that neural progenitor cells exist at the surface of the adult cortex, and, moreover, that ischemia enhances the generation of new inhibitory neurons from these neural progenitor cells. These cells were accordingly named “Layer 1 Inhibitory Neuron Progenitor cells” (L1-INP). However, until now it was not known whether L1-INP-related neurogenesis could be induced in the normal adult cortex.

Tsuyoshi Miyakawa, Koji Ohira, and their colleagues employed fluoxetine, a selective serotonin reuptake inhibitor, and one of the most widely used antidepressants, to stimulate the production of new neurons from L1-INP cells. A large percentage of these newly generated neurons were inhibitory GABAergic interneurons, and their generation coincided with a reduction in apoptotic cell death following ischemia. This finding highlights the potential neuroprotective response induced by this antidepressant drug. It also lends further support to the postulation that induction of adult neurogenesis in cortex is a relevant prevention/treatment option for neurodegenerative diseases and psychiatric disorders.