'ECG For The Mind' Could Diagnose Depression In An Hour

An innovative diagnostic technique invented by a Monash University researcher could dramatically fast-track the detection of mental and neurological illnesses.Monash biomedical engineer Brian Lithgow has developed electrovestibulography which is something akin to an 'ECG for the mind'. Patterns of electrical activity in the brain's vestibular (or balance) system are measured against distinct response patterns found in depression, schizophrenia and other Central Nervous System (CNS) disorders.

The vestibular system is closely connected to the primitive regions of the brain that relate to emotions and behaviour, so Lithgow saw the diagnostic potential of measuring and comparing different patterns of electrovestibular activity.

Working with psychiatry researchers at Monash University's Alfred Psychiatry Research Centre (MAPrc) in Melbourne, Australia, he tested volunteers and found distinct response patterns, or "biomarkers", that distinguished different CNS diseases from each other and from regular electrovestibular activity.

Monash has teamed up with corporate partner Neural Diagnostics to develop and patent electrovestibulography, or EVestG™. It is hoped the simple, quick and inexpensive screening process for CNS diseases will eventually become standard practice in hospitals around the world.

"The patient sits in a specially designed tilt chair that triggers electrical responses in their balance system. A gel-tipped electrode placed in the individual's ear canal silences interfering noise so that these meaningful electrical responses are captured and recorded," the Monash researcher said. "The responses are then compared to the distinct biomarkers indicative of particular CNS disorders, allowing diagnosis to be made in under an hour."

Neural Diagnostics CEO Dr Roger Edwards said the implications of the new technique were huge.

"This could be one of the most significant inventions ever to come out of Monash. CNS disorders cost upwards of $US2 trillion globally and affect one in four people sometime in their lifetime. At present, diagnosing these conditions is done almost exclusively by qualitative measures, through questions and interviews, and it can take many years for sufferers to be correctly diagnosed," Dr Edwards said.

The technique is already attracting international interest and, if further testing goes to plan, it could be adopted in Australian and overseas hospitals within a few years.

"We are doing the necessary research and development and getting independent expert reports done, but results so far are cause for great optimism," Dr Edwards said.

MAPrc Director Professor Jayashri Kulkarni said, "Engineering and psychiatry are two disciplines that do not usually work together, but here at MAPrc, through our collaboration, we are at the forefront of translating biotechnology into clinical tools for psychiatric practice. While there is more work to be done, electrovestibulography could provide a major breakthrough in the diagnosis of mental illnesses".

Brain-behavior Disconnect In Cocaine Addiction

Parts of the brain involved in monitoring behaviors and emotions show different levels of activity in cocaine users relative to non-drug users, even when both groups perform equally well on a psychological test. These results — from a brain-imaging study conducted at the U.S. Department of Energy's Brookhaven National Laboratory and published online the week of May 25, 2009, by the Proceedings of the National Academy of Sciences — suggest that such impairments may underlie addictive vulnerability, and that treatments aimed at improving these functions could help addicted individuals resist drugs."Many studies have found decreased brain activity in drug-addicted individuals relative to healthy control subjects during psychological tests," said lead author Rita Goldstein, a psychologist at Brookhaven Lab. "But it's never been clear if these differences were due to varying levels of interest or ability between the two groups. This is the first study to look at two groups matched for performance and interest — and we still see dramatic differences in the brain regions that play a very significant role in the ability to monitor behavior and regulate emotion, which are both important to resisting drug use.

"Whether these brain differences are an underlying cause or a consequence of addiction, the brain regions involved should be considered targets for new kinds of treatments aimed at improving function and self-regulatory control," Goldstein said.

The researchers studied 17 active cocaine users and 17 demographically matched healthy control subjects. Both groups were trained to push one of four colored buttons corresponding to the color of type used to present words that were either related to drug use (e.g., crack, addict) or neutral household terms. Subjects were given monetary rewards for fast, accurate performance — up to 50 cents for each correct answer on some tests, for a maximum of $75.

After training, both groups performed equally well on this same test while lying in a magnetic resonance imaging (MRI) scanner, with performance improving when they knew they'd be earning the highest monetary reward. During the tests, the scientists used functional MRI (fMRI) to indirectly measure the amount of oxygen being used by specific regions of the brain, as an indicator of brain activity in those regions.

There were three main differences between the cocaine-addicted subjects and the healthy controls:

* The cocaine users had reduced activity in a portion of the anterior cingulate cortex that usually becomes more active (compared to a passive baseline) when monitoring behavior. Activity levels were lowest during the least "interesting," or salient, version of the test — when there was no monetary reward and the words shown were neutral household terms. Within the cocaine-user group, activity levels were lowest in the people who had used cocaine most frequently in the 30 days prior to the test.
* The cocaine users also had reduced activity in another part of the anterior cingulate cortex that usually becomes less active (compared to a passive baseline) when someone is successfully suppressing emotional feelings. Within the cocaine-user group, activity levels during the high-salience version of the test — when each fast, correct answer was rewarded with 50 cents and the words presented were drug-related — were lowest in the people who were most successful in suppressing the task-induced craving. In healthy controls, who did not report craving, activation in this region was not significantly different from baseline.
* The functions within the behavior-monitoring and emotion-monitoring brain regions were interconnected in the healthy control subjects but not in the addicted individuals. In all, these group differences in brain function and interconnectivity were quite robust and all the more meaningful in that there were no differences between the groups in performance on or interest ratings for the task.

"When you really have to suppress a powerful negative emotion, like sadness, anxiety or drug craving, activity in this brain region is supposed to decrease, possibly to tune out the background 'noise' of these emotions so you can focus on the task at hand," Goldstein said.

"Our results show that activity in this region indeed went down in the drug-using group, suggesting they were actively trying to suppress craving. Indeed subjects who reported the highest levels of task-induced craving were the least able to suppress activity in this particular brain region.

"This could be because these drug users were still being distracted by background 'noise' stimuli, like memories of having taken drugs or anticipation of further use," Goldstein said.

"This work gives us some clues as to what happens when drug users are unable to suppress craving — and how that might work together with a decreased ability to monitor behavior, even during neutral, non-emotional situations, to make some people more vulnerable to taking drugs," Goldstein said.

The findings point to the importance of improving activity in the behavior-monitoring brain region, possibly by using behavioral and pharmacological approaches to increase motivation and top-down monitoring. Treatments aimed at strengthening activity in the emotion-monitoring brain region may further help addicted individuals regain self-control, especially during hard to suppress highly emotional situations (e.g., during craving). Treatments aimed at strengthening the interconnectivity between these brain regions may decrease impulsivity.

This study was supported by grants from the National Institute on Drug Abuse and the General Clinical Research Center of Stony Brook University.

Sleep May Help Clear Brain For New Learning

A new theory about sleep's benefits for the brain gets a boost from fruit flies in the journal Science. Researchers at Washington University School of Medicine in St. Louis found evidence that sleep, already recognized as a promoter of long-term memories, also helps clear room in the brain for new learning.The critical question: How many synapses, or junctures where nerve cells communicate with each other, are modified by sleep? Neurologists believe creation of new synapses is one key way the brain encodes memories and learning, but this cannot continue unabated and may be where sleep comes in.

"There are a number of reasons why the brain can't indefinitely add synapses, including the finite spatial constraints of the skull," says senior author Paul Shaw, Ph.D., assistant professor of neurobiology at Washington University School of Medicine in St. Louis. "We were able to track the creation of new synapses in fruit flies during learning experiences, and to show that sleep pushed that number back down."

Scientists don't yet know how the synapses are eliminated. According to theory, only the less important connections are trimmed back, while connections encoding important memories are maintained.

Many aspects of fly sleep are similar to human sleep; for example, flies and humans deprived of sleep one day will try to make up for the loss by sleeping more the next day. Because the human brain is much more complex, Shaw uses the flies as models for answering questions about sleep and memory.

Sleep is a recognized promoter of learning, but three years ago Shaw turned that association around and revealed that learning increases the need for sleep in the fruit fly. In a 2006 paper in Science, he and his colleagues found that two separate scenarios, each of which gave the fruit fly's brain a workout, increased the need for sleep.

The first scenario was inspired by human research linking an enriched environment to improved memory and other brain functions. Scientists found that flies raised in an enhanced social environment—a test tube full of other flies—slept approximately 2-3 hours longer than flies raised in isolation.

Researchers also gave male fruit flies their first exposure to female fruit flies, but with a catch—the females were either already mated or were actually male flies altered to emit female pheromones. Either fly rebuffed the test fly's attempts to mate. The test flies were then kept in isolation for two days and exposed to receptive female flies. Test flies that remembered their prior failures didn't try to mate again; they also slept more. Researchers concluded that these flies had encoded memories of their prior experience, more directly proving the connection between sleep and new memories.

Scientists repeated these tests for the new study, but this time they used flies genetically altered to make it possible to track the development of new synapses, the junctures at which brain cells communicate.

"The biggest surprise was that out of 200,000 fly brain cells, only 16 were required for the formation of new memories, " says first author Jeffrey Donlea, a graduate student. "These sixteen are lateral ventral neurons, which are part of the circadian circuitry that let the fly brain perform certain behaviors at particular times of day."

When flies slept, the number of new synapses formed during social enrichment decreased. When researchers deprived them of their sleep, the decline did not occur.

Donlea identified three genes essential to the links between learning and increased need for sleep: rutabaga, period and blistered. Flies lacking any of those genes did not have increased need for sleep after social enrichment or the mating test.

Blistered is the fruit fly equivalent to a human gene known as serum response factor (SRF). Scientists have previously linked SRF to plasticity, a term for brain change that includes both learning and memory and the general ability of the brain to rewire itself to adapt to injury or changing needs.

The new study shows that SRF could offer an important advantage for scientists hoping to study plasticity: unlike other genes connected to plasticity, it's not also associated with cell survival.

"That's going to be very helpful to our efforts to study plasticity, because it removes a large confounding factor," says co-author Naren Ramanan, Ph.D., assistant professor of neurobiology. "We can alter SRF activity and not have to worry about whether the resulting changes in brain function come from changes in plasticity or from dying cells."

Shaw plans further investigations of the connections between memory and sleep, including the question of how increased synapses induce the need for sleep.

"Right now a lot of people are worried about their jobs and the economy, and some are no doubt losing sleep over these concerns," Shaw says. "But these data suggest the best thing you can do to make sure you stay sharp and increase your chances of keeping your job is to make getting enough sleep a top priority."

Teenage Boys Who Eat Fish At Least Once A Week Achieve Higher Intelligence Scores

Fifteen-year-old males who ate fish at least once a week displayed higher cognitive skills at the age of 18 than those who it ate it less frequently, according to a study of nearly 4,000 teenagers published in the March issue of Acta Paediatrica.Eating fish once a week was enough to increase combined, verbal and visuospatial intelligence scores by an average of six per cent, while eating fish more than once a week increased them by just under 11 per cent.

Swedish researchers compared the responses of 3,972 males who took part in the survey with the cognitive scores recorded in their Swedish Military Conscription records three years later.

"We found a clear link between frequent fish consumption and higher scores when the teenagers ate fish at least once a week" says Professor Kjell Torén from the Sahlgrenska Academy at the University of Gothenburg, one of the senior scientists involved in the study. "When they ate fish more than once a week the improvement almost doubled.

"These findings are significant because the study was carried out between the ages of 15 and 18 when educational achievements can help to shape the rest of a young man's life."

The research team found that:

* 58 per cent of the boys who took part in the study ate fish at least once a week and a further 20 per cent ate fish more than once a week.
* When male teenagers ate fish more than once a week their combined intelligence scores were on average 12 per cent higher than those who ate fish less than once a week. Teenagers who ate fish once a week scored seven per cent higher.
* The verbal intelligence scores for teenagers who ate fish more than once a week were on average nine per cent higher than those who ate fish less than once a week. Those who ate fish once a week scored four per cent higher.
* The same pattern was seen in the visuospatial intelligence scores, with teenagers who ate fish more than once a week scoring on average 11 per cent higher than those who ate fish less than once a week. Those who ate fish once a week scored seven per cent higher.

"A number of studies have already shown that fish can help neurodevelopment in infants, reduce the risk of impaired cognitive function from middle age onwards and benefit babies born to women who ate fish during pregnancy" says Professor Torén.

"However we believe that this is the first large-scale study to explore the effect on adolescents."

The exact mechanism that links fish consumption to improved cognitive performance is still not clear.

"The most widely held theory is that it is the long-chain polyunsaturated fatty acids found in fish that have positive effects on cognitive performance" explains Professor Torén.

"Fish contains both omega-3 and omega-6 fatty acids which are known to accumulate in the brain when the foetus is developing. Other theories have been put forward that highlight their vascular and anti-inflammatory properties and their role in suppressing cytokines, chemicals that can affect the immune system."

In order to isolate the effect of fish consumption on the study subjects, the research team looked at a wide range of variables, including ethnicity, where they lived, their parents' educational level, the teenagers' well-being, how frequently they exercised and their weight.

"Having looked very carefully at the wide range of variables explored by this study it was very clear that there was a significant association between regular fish consumption at 15 and improved cognitive performance at 18" concludes lead author Dr Maria Aberg from the Centre for Brain Repair and Rehabilitation at the University of Gothenburg.

"We also found the same association between fish and intelligence in the teenagers regardless of their parents' level of education."

The researchers are now keen to carry out further research to see if the kind of fish consumed - for example lean fish in fish fingers or fatty fish such as salmon - makes any difference to the results.

"But for the time being it appears that including fish in a diet can make a valuable contribution to cognitive performance in male teenagers" says Dr Aberg.

Evidence Appears To Show How And Where Brain's Frontal Lobe Works

A Brown University study of stroke victims has produced evidence that the frontal lobe of the human brain controls decision-making along a continuum from abstract to concrete, from front to back.Abstract actions can be controlled at an abstract level, such as deciding to make a sandwich, or at more concrete and specific levels, such as choosing a sequence of movements that make the sandwich.

The scientific data supports preexisting theories that abstract decisions about action take place in the front of the frontal lobe, the back portion controls the capacity for concrete decisions, and the progression from front to back forms a gradient from abstract to concrete.

The Brown researchers are among the first to show that specific areas of the frontal cortex are needed for different levels of abstract decision.

The finding, to be detailed March 1 in the journal Nature Neuroscience, represents a huge leap in comprehending how the brain supports higher level cognition and intelligent behavior. It could lead to advances in everything from the treatment of strokes to understanding how humans develop thought. Researchers from the University of California–Berkeley also participated in the study.

“It is among the strongest evidence to date for a systemic organization of the frontal cortex,” said lead author David Badre, an assistant professor of cognitive and linguistic sciences at Brown University.

The frontal cortex of brain has been long known to affect the internal control of behavior. It controls the capacity to plan, reason, conduct higher-level thinking and connect what we know about the world to how we behave.

Badre and his collaborators came to their conclusion by studying stroke victims who suffered damage to different parts of the frontal lobe. The patients all suffered a stroke at least six months prior to testing. All were screened with an MRI or CT scan to determine where any lesions existed in the brain post-stroke.

The scientists recruited 11 patients — seven men and four women, ranging from age 45 to 73. A 12th patient was recruited but could not perform any of the tests involved.

Researchers gave the patients four different tests that ultimately required selecting a finger-press response. For example, the first test would show a color such as red, which required an index finger push. Blue would trigger the middle finger. The test would then become more difficult by adding more alternate finger presses.

Patients faced greater challenges in selecting a response as subsequent, progressive tests became more complex, with more abstract options.

Badre and colleagues found that damage at a given location affected more abstract decisions but left intact the capacity for more concrete decisions. “If there is damage in a given spot, it will affect all higher (decision-making) functions but not lower functions,” Badre said.

The National Institutes of Health, Veterans Administration Research Service and a National Research Service Award supported the research.

Mesh-like Network Of Arteries Adjusts To Restore Blood Flow To Stroke-injured Brain

A grid of small arteries at the surface of the brain redirects flow and widens at critical points to restore blood supply to tissue starved of nutrients and oxygen following a stroke, a new study has found.

“This is optimistic news,” said David Kleinfeld, a physics professor at the University of California, San Diego, whose group studies blood flow in animal models of stroke.

Damage from stroke can continue for hours or even days as compromised brain tissue surrounding the core injury succumbs to deprivation of oxygen and nutrients.

“This is the area doctors are trying to protect after a stroke,” said Andy Shih, a postdoctoral fellow in Kleinfeld’s group who conducted the experiments. “Those neurons are teetering on the edge of death and survival.”

Previous work with animal models had found that blood flow can persistently slow in the aftermath of a stroke, which would hinder the delivery of drugs that might help recovery. But those studies only measured the speed of the blood.

By measuring both the speed of blood cells moving through individual small arteries and the diameters of the same vessels, the scientists found that the arteries dilate to maintain a constant delivery of blood cells.

“You find that the velocity has gone down, but that the diameter—on average—exactly compensates,” Kleinfeld said.

Patrick Drew and Philbert Tsai in Kleinfeld’s group, and Beth Friedman and Patrick Lyden, MD, of the neuroscience department at UC San Diego’s School of Medicine co-authored the paper. Lyden, whose contributions to a 1995 study proved that the drug tPA can reverse the course of stroke when administered promptly, also directs the UC San Diego Stroke Center. The Journal of Cerebral Blood Flow and Metabolism published their new finding online January 28.

Key to this resilience, it seems, is the structure of the vascular network overlying the brain.

“Vessels on the surface of the brain have a mesh-like architecture,” Kleinfeld said. “One consequence of that is that it operates like a grid system that redistributes “current flow as you need it.”

“City traffic freezes a lot less than you would think because once a street gets bogged down, you can move over to another street,” he said. “This seems to be what happens on the surface of the brain.”

Flows through the surface vessels reversed and stalled, as previously observed, but those changes helped to redistribute blood to ensure a steady supply though vessels that penetrate into the brain.

Shih focused his measurements on small arteries, called arterioles, at the point where they dive into the brain to supply a discrete patch of the cortex, a juncture that is vulnerable to occlusions that can cause microstrokes this group’s previous work has found.

“These are extremely important. A single penetrating arteriole will feed a column of tissue,” Shih said. “These are bottlenecks in flow.”

The penetrating vessels neither reversed nor stalled, even though many connected to loops and bridges in the vascular network that could have allowed that to happen. Even when the pressure dropped permanently as a result of stroke damage, wider lanes allowed the network to deliver red blood cells at the same rate.

“Diameter is the major determinant to how blood actually flows through vessels. Open up a blood vessel a little bit and you’ll have a huge change in the amount of blood that goes through,” Shih said. “Blood flow comes back, and it seems that these vessels are very resistant to the stroke. They function quite normally.”

The work was funded by the Canadian Institutes of Health Research, National Institutes of Health, National Science Foundation and Veterans Medical Research Foundation.

Women's Brains Recognize, Encode Smell Of Male Sexual Sweat

A new Rice University study published in the Journal of Neuroscience found that socioemotional meanings, including sexual ones, are conveyed in human sweat.

Denise Chen, assistant professor of psychology at Rice, looked at how the brains of female volunteers processed and encoded the smell of sexual sweat from men. The results of the experiment indicated the brain recognizes chemosensory communication, including human sexual sweat.

Scientists have long known that animals use scent to communicate.

Chen's study represents an effort to expand knowledge of how humans’ sense of smell complement their more powerful senses of sight and hearing.

The experiment directly studied natural human sexual sweat using functional magnetic resonance imaging (fMRI). Nineteen healthy female subjects inhaled olfactory stimuli from four sources, one of which was sweat gathered from sexually aroused males.

The research showed that several parts of the brain are involved in processing the emotional value of the olfactory information. These include the right fusiform region, the right orbitofrontal cortex and the right hypothalamus.

"With the exception of the hypothalamus, neither the orbitofrontal cortex nor the fusiform region is considered to be associated with sexual motivation and behavior," Chen said. "Our results imply that the chemosensory information from natural human sexual sweat is encoded more holistically in the brain rather than specifically for its sexual quality."

Humans are evolved to respond to salient socioemotional information.

Distinctive neural mechanisms underlie the processing of emotions in facial and vocal expressions. The findings help explain the neural mechanism for human social chemosignals.

The understanding of human smell at the neural level is still at the beginning stage. The present work is the first fMRI study of human social chemosignals.

The research, co-authored by Chen and Wen Zhou, graduate student in the Psychology Department, appeared in the December 31 issue of Journal of Neuroscience.

The research was supported in part by the National Institutes of Health.

Scientists See Brain Aging Before Symptoms Appear

UCLA scientists have used innovative brain-scan technology developed at UCLA, along with patient-specific information on Alzheimer's disease risk, to help diagnose brain aging, often before symptoms appear. Published in the January issue of Archives of General Psychiatry, their study may offer a more accurate method for tracking brain aging.

Researchers used positron emission tomography (PET), which allows "a window into the brain" of living people and specifically reveals plaques and tangles, the hallmarks of neurodegeneration. The PET scans were complemented by information on patients' age and congnitive status and a genetic profile.

"Combining key patient information with a brain scan may give us better predictive power in targeting those who may benefit from early interventions, as well as help test how well treatments are working," said study author Dr. Gary Small, who holds UCLA's Parlow-Solomon Chair on Aging and is a professor at the Semel Institute for Neuroscience and Human Behavior at UCLA.

Scientists took PET brain scans of 76 non-demented volunteers after they had been intravenously injected with a new chemical marker called FDDNP, which binds to plaque and tangle deposits in the brain. Researchers were then able to pinpoint where these abnormal protein deposits were accumulating.

They reported that older age correlated with higher concentrations of FDDNP in the medial and lateral temporal regions of the brain, areas involved with memory, where plaques and tangles usually collect. The average age of study volunteers was 67.

Thirty-four of the 76 volunteers carried the APOE-4 gene allele, which heightens the risk for developing Alzheimer's disease. This group demonstrated higher FDDNP levels in the frontal region of the brain, also involved in memory, than study participants without allele.

"We found that for many volunteers, the imaging scans reflected subtle brain changes, which take place before symptoms manifest," said Small, who is also director of the UCLA Center on Aging.

Small noted that the brain will try to compensate for any problems, which is why cognitive symptoms may not become apparent until much later.

"This type of scan offers an opportunity to see what is really going on in the brain," he said.

Another subset of the volunteers had mild cognitive impairment (MCI), a condition that increases the risk of developing Alzheimer's disease. These 36 volunteers had higher measures of FDDNP in the medial temporal brain regions than normal volunteers. Those who had both MCI and the APOE-4 gene had higher concentrations of FDDNP in the medial temporal brain regions than volunteers who had MCI but not APOE-4.

"We could see more advancing disease in those with mild cognitive impairment, who are already demonstrating some minimal symptoms," Small said. "Eventually, this imaging method, together with patient information like age, cognitive status and genetics, may help us better manage brain aging."

According to Small, in the future, brain aging may be controlled similarly to high cholesterol or high blood pressure. Patients would receive a brain scan and perhaps a genetic test to predict their risk. Medications and other interventions could be prescribed, if necessary, to prevent or delay future neurodegeneration, allowing doctors to protect a healthy brain before extensive damage occurs. The brain scans may also prove helpful in tracking the effectiveness of treatments.

PET, combined with the FDDNP probe, is the only imaging technology that offers a full profile of neurodegeneration that includes measures of both plaques and tangles — the physical evidence of Alzheimer's disease in the brain.

"The fact that we can see tau tangles as well as amyloid plaques is critically important in early detection of brain aging, since the tangles are the first abnormal proteins that appear in the brain, long before dementia is clinically obvious to the physician," said Dr. Jorge R. Barrio, a study author and professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA.

Such subtleties allow more insight into how the plaques and tangles spread and ultimately how Alzheimer's disease may develop.

Currently, the new FDDNP-PET scans are used in a research setting, but clinical trials are in development to bring the technology to wider patient use.

The study was funded by both government and nonprofit agencies, including the National Institutes of Health, the U.S. Department of Energy, the Ahmanson Foundation, the Larry L. Hillblom Foundation and the Tamkin Foundation.

Additional UCLA authors include Prabha Siddarth, Ph.D.; Alison C. Burggren, Ph.D.; Linda M. Ercoli, Ph.D.; Karen J. Miller, Ph.D.; Dr. Helen Lavretsky; and Susan Y. Bookheimer, Ph.D, all from the UCLA Department of Psychiatry and Biobehavioral Sciences and the Semel Institute for Neuroscience and Human Behavior at UCLA; Vladimir Kepe, Ph.D.; S.C. Huang, Ph.D.; and Michael E. Phelps, Ph.D. from the UCLA Department of Molecular and Medical Pharmacology; and Paul M. Thompson, Ph.D., and Greg M. Cole, Ph.D., from the UCLA Department of Neurology.