Connectome map more than doubles human cortex’s known regions

Researchers have mapped 180 distinct areas in our brain’s outer mantle, or cortex - more than twice the number previously known. They have also developed software that automatically detects the “fingerprint” of each of these areas in an individual’s brain scans.

Funded by the US National Institutes of Health through its Human Connectome Project (HCP), this software correctly mapped the areas by incorporating data from multiple non-invasive brain imaging measures that corroborated each other.

“These new insights and tools should help to explain how our cortex evolved and the roles of its specialized areas in health and disease, and could eventually hold promise for unprecedented precision in brain surgery and clinical work-ups,” said Bruce Cuthbert, PhD, acting director of NIH’s National Institute of Mental Health (NIMH), which co-funded the research as part of the HCP.

The new study identified – with a nearly 97% detection rate – 97 new cortex areas per hemisphere, in addition to confirming 83 that were previously known. The findings are reported in the July 20, 2016 issue of Nature.

Earlier studies of cortex organization often used just one measure, such as examining postmortem tissue with a microscope. Uncertain delineation of cortex areas has sometimes led to shaky comparability of brain imaging findings.

“The situation is analogous to astronomy where ground-based telescopes produced relatively blurry images of the sky before the advent of adaptive optics and space telescopes,” noted Glasser, lead author of the study.

The HCP team set out to banish this blurriness by using multiple, precisely aligned, magnetic resonance imaging (MRI) modalities to measure cortical architecture, activity, connectivity, and topography in a group of 210 healthy participants. These measures – including cortex thickness, cortex myelin content, task and resting-state functional MRI (fMRI) – cross-validated each other. The findings were, in turn, confirmed in an additional independent sample of 210 healthy participants.

Even though some cortex areas turned out to be atypically located in a small minority of subjects, the data-derived algorithms incorporated into the software were able to successfully map them. While the study included fMRI scans of subjects performing tasks, the researchers determined that resting-state MRI techniques should suffice to map the areas in future studies using the tools they developed. Some areas may turn out to have further subdivisions or be subunits of other areas, in light of new data, noted senior author Van Essen.

“The ability to discriminate individual differences in the location, size, and topology of cortical areas from differences in their activity or connectivity should facilitate understanding of how each property is related to behaviour and genetic underpinnings,” added Glasser.

The automated “areal classifier” and related tools are being shared with the research community via HCP websites In addition, the extensively analyzed data underlying each of the published figures can be accessed via an NIH-funded database developed in the Van Essen laboratory

BMI significantly better than fat percentage in predicting death from CVD

An international study led by the University of Granada has determined that the measurement of obesity should include both fat and muscle for a given height and not just excess body fat alone.

In the study, the authors considered whether an accurate measurement of body fat was a more powerful predictor of death from cardiovascular disease than the cheap, fast and simple BMI measurement. To the surprise of many BMI was significantly better than fat percentage in predicting future death from cardiovascular disease.

The researchers analyzed data of more than 60,000 people who were examined over an average of 15 years. The goal was to study how factors such as obesity can predict the risk of dying from cardiovascular disease.

The study was coordinated by Francisco B. Ortega, a Ramón y Cajal researcher at the Faculty of Physical Activity and Sports Sciences at UGR and published in the prestigious American journal Mayo Clinic Proceedings.

The team worked in collaboration with respected American researchers epidemiologist Steven N. Blair and cardiologist Charles J. Lavie.

The researchers worked with data from the Aerobics Center Longitudinal Study (ACLS) carried out by the Cooper Institute in Texas, USA. The study, which began in the 1970s, tracked more than 60,000 participants over an average of 15 years. The objective was to study how factors like obesity can predict the risk of dytheing from cardiovascular disease.

Unlike most longitudinal studies of this kind, the researchers in the present study measured not only the weight and height but also the amount of fat and muscle of the participants. The weight and height measurements allowed them to calculate the body mass index (BMI=weight (kg) divided by height (m)2). To measure fat and muscle, they used skin fold measurements and, in a subsample of more than 30,000 participants, they used hydrostatic weight testing which is considered a gold-standard in the measurement of body fat.

The concept of BMI was first proposed in 1832 by Adolphe Quetelet and is used internationally to define when a person is overweight (BMI.25kg/m2) or obese (BMI.30kg/m2). It has now been used in more than 100,000 published scientific articles, making it the most widely used anthropometric index in the world.

"Nevertheless, BMI is subject to a great deal of heavy criticism due to its inability to discriminate whether a high body weight is due to the person having an excess of fat, muscle or both. Many authors propose using a percentage of fat rather than the BMI, especially when studying with regard to cardiovascular disease," explains UGR researcher Francisco B. Ortega.

In the study, BMI was show to be significantly better than fat percentage in predicting future death from cardiovascular disease.

Furthermore, even when the analysis was restricted to half of the sample (30,000 people), measuring body fat through hydrostatic weight testing, which is an extremely complex and expensive method, BMI was still the best predictor of mortality from cardiovascular causes.

How is it possible that BMI, which measures both fat and muscle relative to height, can predict cardiovascular disease better than accurate indicators of the amount of fat that a person has? 

"We considered that a possible hypothesis could be that not only are large amounts of fat associated with greater risk, but also great amounts of muscle or other weight unrelated to fat," says Ortega.

Scientists at UGR tested the hypothesis with data from the study and it was confirmed. This would explain that BMI, which is the sum of fat and muscle relative to height, is a better predictor, at an epidemiological level, of future cardiovascular disease than indicators of the amount of fat alone. In the study, the authors offer different physiological elements that can help to explain the results.

The study offers significant new results which are nearly contradictory to existing beliefs. It also roundly supports the use of BMI in large epidemiological studies and contributes to a better understanding of obesity and its relationship to cardiovascular disease.

  • doi: 10.1016/j.mayocp.2016.01.008

A virtual brain helps decrypt epilepsy

A virtual brain helps decrypt epilepsy Researchers at CNRS, INSERM, Aix- Marseille University and AP-HM have created a virtual brain that can reconstitute the brain of a person affected by epilepsy for the first time. The research enables a better understanding of how the disease works and can also better prepare for surgery. The results are published in Neuroimage, July 28, 2016.

Worldwide, one percent of the population suffers from epilepsy. The disease affects individuals differently, so personalized diagnosis and treatment are important. Currently we have few ways to understand the pathology’s mechanisms of action, and mainly use visual interpretation of an MRI and electroencephalogram. This is especially difficult because 50% of patients do not present anomalies visible in MRI, so the cause of their epilepsy is unknown.

Researchers have succeeded for the first time in developing a personalized virtual brain, by designing a base “template” and adding individual patient information, such as the specific way the brain’s regions are organized and connected in each individual. Mathematical models that cause cerebral activity can be tested on the virtual brain. In this way, scientists have been able to reproduce the place where epilepsy seizures initiate and how they propagate. This brain therefore has real value in predicting how seizures occur in each patient, which could lead to much more precise diagnosis.

Moreover, 30% of epileptic patients do not respond to drugs, so their only hope remains surgery. This is effective if the surgeon has good indications of where to operate. The virtual brain gives surgeons a virtual “platform”. In this way they can determine where to operate while avoiding invasive procedures, and especially prepare for the operation by testing different surgical possibilities, seeing which would be most effective and what the consequences would be, something that is obviously impossible to do on the patient.

In the long run, the team’s goal is to provide personalized medicine for the brain, by offering virtual, tailored, therapeutic solutions that are specific for each patient. The researchers are currently working on clinical trials to demonstrate the predictive value of their discovery. This technology is also being tested on other pathologies that affect the brain, such as strokes, Alzheimer’s, degenerative neurological diseases, and multiple sclerosis.

This work involves researchers at the Institut de Neurosciences des Systèmes (INSERM/AMU), the Centre de Résonance Magnétique Biologique et Médicale (CNRS/AMU/AP-HM), the Département Epileptologie et du Département Neurophysiologie Clinique at AP-HM, and the Epilepsy Center of Cleveland. It was done in the Fédération Hospitalo- Universitaire Epinext.

  • doi: 10.1016/j.neuroimage.2016.04.049

New study explains why MRSA kills influenza patients

Researchers have discovered that secondary infection with the Methicillinresistant Staphylococcus aureus (MRSA) bacterium often kills influenza patients because the flu virus alters the antibacterial response of white blood cells, causing them to damage the patients’ lungs instead of destroying the bacterium. The study, was is published online 15 August 2016 in The Journal of Experimental Medicine, suggests that inhibiting this response may help treat patients infected with both the flu virus and MRSA.

Many influenza patients develop severe pneumonia as a result of secondary infections with MRSA. Over half of these patients die, even when treated with antibiotics that are usually capable of clearing MRSA infections.

Keer Sun, an assistant professor at the University of Nebraska Medical Center, previously discovered that mice infected with influenza are susceptible to MRSA because the ability of their macrophages and neutrophils to kill bacteria by releasing hydrogen peroxide and other reactive oxygen species is suppressed. But it remained unclear why MRSA-infected influenza patients often die, even after receiving an appropriate antibiotic treatment.

Sun and colleagues now reveal that this may be because the patients’ white blood cells cause extensive damage to their lungs. Though the macrophages and neutrophils of mice co-infected with influenza and MRSA were defective at killing bacteria, reactive oxygen species released by these cells induced the death of inflammatory cells within the lungs, lethally damaging the surrounding tissue. Inhibiting NADPH oxidase 2 (Nox2), the enzyme that produces reactive oxygen species in macrophages and neutrophils, reduced the extent of this damage and, when combined with antibiotic treatment, boosted the survival of co-infected mice.

“Our results demonstrate that influenza infection disrupts the delicate balance between Nox2-dependent antibacterial immunity and inflammation,” says Sun. “This not only leads to increased susceptibility to MRSA infection but also extensive lung damage. Treatment strategies that target both bacteria and reactive oxygen species may significantly benefit patients with influenza-complicated MRSA pneumonia.”

  • doi: 10.1084/jem.20150514


Researchers discover bacteria from human nose produces novel antibiotic effective against multi-resistant pathogens

Scientists at the University of Tübingen and the German Center for Infection Research (DZIF) have discovered that Staphylococcus lugdunensis which colonizes in the human nose produces a previously unknown antibiotic. As tests on mice have shown, the substance which has been named Lugdunin is able to combat multiresistant pathogens, where many classic antibiotics have become ineffective. The research results are published in the 27 July 2016 issue of Nature.

Infections caused by antibiotic-resistant bacteria – like the pathogen Staphylococcus aureus (MRSA) which colonizes on human skin – are among the leading causes of death worldwide. The natural habitat of harmful Staphylococcus bacteria is the human nasal cavity. In their experiments, Dr Bernhard Krismer, Alexander Zipperer and Professor Andreas Peschel from the Interfaculty Institute for Microbiology and Infection Medicine Tübingen (IMIT) observed that Staphylococcus aureus is rarely found when Staphylococcus lugdunensis is present in the nose.

“Normally antibiotics are formed only by soil bacteria and fungi,” says Professor Andreas Peschel. “The notion that human microflora may also be a source of antimicrobial agents is a new discovery.” In future studies, scientists will examine whether Lugdunin could actually be used in therapy. One potential use is introducing harmless Lugdunin-forming bacteria to patients at risk from MRSA as a preventative measure.

Researchers from the Institute of Organic Chemistry at the University of Tübingen closely examined the structure of Lugdunin and discovered that it consists of a previously unknown ring structure of protein blocks and thus establishes a new class of materials.

Antibiotic resistance is a growing problem for physicians. “There are estimates which suggests that more people will die from resistant bacteria in the coming decades than cancer,” says Dr Bernhard Krismer. “The improper use of antibiotics strengthens this alarming development” he continues. As many of the pathogens are part of human microflora on skin and mucous membranes, they cannot be avoided. Particularly for patients with serious underlying illnesses and weakened immune systems they represent a high risk – these patients are easy prey for the pathogens. Now the findings made by scientists at the University of Tübingen open up new ways to develop sustainable strategies for infection prevention and to find new antibiotics – also in the human body.

  • doi: 10.1038/nature18634

Handheld device takes high-resolution images of children’s retinas

Engineers and physicians at Duke University have developed a handheld device capable of capturing images of a retina with cellular resolution. The new probe will allow researchers to gather detailed structural information about the eyes of infants and toddlers for the first time.

“Diagnostic tools that examine and image the retina have been well-designed for adults, but are exceedingly difficult to use in infants and young children who can’t hold the required position or focus for long enough periods of time,” said Cynthia Toth, professor of ophthalmology and biomedical engineering at Duke University. “Before now, it hasn’t been possible to measure the impact of injury or diseases on their photoreceptors, the cells in the eye in which light is first converted into nerve signals.”

The eye presents a unique opportunity for research and imaging. It is not difficult to access, it is relatively self-contained,improvements in function are easily measured and there is even a natural opening to peer inside. But it is also delicate, with important structures buried millimetres below its various surfaces, so a wide range of technologies are needed to study it.

Over the past three decades, one of the most popular of these has been optical coherence tomography (OCT). By shining specific frequencies of light into the eye’s tissues and comparing those reflections to identical but unimpeded light waves, researchers can build 3D images several millimetres deep of the back of the eye.

The equipment, however, has traditionally been bulky, meaning the patient must sit still in front of the machine and remain focused on a particular point. And the process takes tens of minutes – an eternity to most toddlers, as any parent knows well.

While handheld devices based on OCT and other technologies have been developed before, they are far from ideal. Some weigh several pounds, making holding them still over a child’s eye tiresome and difficult, and none provide a high enough resolution to see individual photoreceptors.

In a new paper, published online on August 1, 2016, in Nature Photonics, researchers and ophthalmologists from Duke University present a new option. Their handheld device is about the size of a pack of cigarettes, weighs no more than a few slices of bread and is capable of gathering detailed information about the retina’s cellular structure.

“This paper demonstrates the first time researchers have been able to directly measure the density of photoreceptors called cones in infants,” said Joseph Izatt, the Michael J. Fitzpatrick Professor of Engineering at Duke and a pioneer of OCT technology. “As such, it opens the door to new research that will be key in future diagnosis and care of hereditary diseases.”

Without the ability to gather this sort of information, there is little to no data about how a child’s retina develops, as it matures by the age of 10. This limits our knowledge of how diseases affect a child’s vision early in life and makes diagnosis of these diseases more difficult.

In the paper, a collaborative research group led by Izatt, Sina Farsiu, professor of ophthalmology and biomedical engineering at Duke, and Toth, detail the developments that made their new handheld device possible.

A new type of smaller scanning mirror recently reached a point where it could replace larger, older models. A new design using converging rather than collimated light cut the telescoping length of the device by a third. Custom lenses detailing curvature, thickness and glass type were designed by first author Francesco LaRocca and specially fabricated. And a mechanical design to hold and integrate the components was designed by Derek Nankivil – who, with LaRocca, recently graduated with their PhDs from Duke – and fabricated in a machine shop on Duke’s campus.

The new device was then given to clinicians for testing on adults, which proved that it was capable of getting accurate photoreceptor density information. It was also used for research imaging in children who were already having an eye exam under anaesthesia.

“But because children have never been imaged with these systems before, there’s no gold standard that we can compare it to,” said LaRocca. “The results do, however, match theories of how cones migrate as the eye matures. The tests also showed different microscopic pathological structures that are not normally possible to see with current lower-resolution clinical-grade handheld systems.”

With the prototype being used by clinicians at Duke Health, the amount of information being gained from children’s scans could eventually create a database to give a much better picture of how the retina matures with age.

  • doi: 10.1038/NPHOTON.2016.141

Breastfeeding associated with better brain development and neurocognitive outcomes

A new study, which followed 180 pre-term infants from birth to age seven, found that babies who were fed more breast milk within the first 28 days of life had larger volumes of certain regions of the brain at term equivalent and had better IQs, academic achievement, working memory, and motor function.

The findings were published 29 July 2016 in The Journal of Pediatrics.

“Our data support current recommendations for using mother’s milk to feed preterm babies during their neonatal intensive care unit (NICU) hospitalization. This is not only important for moms, but also for hospitals, employers, and friends and family members, so that they can provide the support that’s needed during this time when mothers are under stress and working so hard to produce milk for their babies,” says Mandy Brown Belfort, MD, a researcher and physician in the Department of Newborn Medicine at Brigham and Women’s Hospital and lead author.

Researchers studied infants born before 30 weeks’ gestation that were enrolled in the Victorian Infant Brain Studies cohort from 2001-2003. They determined the number of days that infants received breast milk as more than 50% of their nutritional intake from birth to 28 days of life. Additionally, researchers examined data related to regional brain volumes measured by magnetic resonance imaging (MRI) at each baby’s term equivalent age and at seven years old, and also looked at cognitive (IQ, reading, mathematics, attention, working memory, language, visual perception) and motor testing at age seven.

The findings show that, across all babies, infants who received predominantly breast milk on more days during their NICU hospitalization had larger deep nuclear grey matter volume, an area important for processing and transmitting neural signals to other parts of the brain, at term equivalent age, and by age seven, performed better in IQ, mathematics, working memory, and motor function tests. Overall, ingesting more human milk correlated with better outcomes, including larger regional brain volumes at term equivalent and improved cognitive outcomes at age 7.



Date of upload: 15th Sep 2016

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