The Importance of Nutrition During Pregnancy for Brain Development

The Lifelong Importance of Nutrition in Pregnancy for Brain Development

Susanne D. Rooij

How drastic is the effect of nutrition during pregnancy on infant brain development? -JR

The importance of a healthy diet for proper functioning of the brain is increasingly being recognized. Week in, week out studies appear recommending a high intake of certain foods in order to achieve optimal brain function and prevent brain diseases. Although it is definitely no punishment for the most of us to increase our chocolate consumption to boost brain function, the most important period during which nutrition affects our brain may already be behind us.

Nutrition affects the brain throughout life, but it is potentially most important during the critical prenatal period, during which the lion’s share of our brain development takes place. During the time we spend in the womb, our brains undergo dramatic changes. The fetal nervous system from which the brain and spinal cord progress is one of the first systems to develop. Its foundations are laid down during the very first days of pregnancy. At the end of pregnancy, the brain has grown exponentially and is capable of learning and forming memories. It is actually not very hard to imagine that to lay a good foundation for the brain it is of utmost importance to receive the best building blocks through proper nutrition of the mother.

A very dramatic illustration of the consequences of not receiving adequate nutrition was shown in a study from the seventies in which Zena Stein and colleagues investigated the effects of prenatal exposure to the Dutch famine on the development of babies. The Dutch ‘Hungerwinter’ was a period of severe famine that struck the Western part of the Netherlands at the end of World War II. There was so little food available that even pregnant women suffered from severe undernutrition. Stein and her colleagues found that babies that had been exposed to the famine during the first trimester of pregnancy had increased rates of birth defects of the central nervous system.

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Babies use expectations about what they perceive to shape their brains

A study show that infants can use what they perceive and their expectations about what they perceive to develop their brains.

Infants can use their expectations about the world to rapidly shape their developing brains, researchers have found.

A series of experiments with infants ages 5 to 7 months has shown that portions of babies' brains responsible for visual processing respond not just to the presence of visual stimuli, but also to the mere expectation of visual stimuli, according to the researchers from Princeton University, the University of Rochester and the University of South Carolina.

That type of sophisticated neural processing was once thought to happen only in adults and not infants, whose brains are still developing important neural connections.

"We show that in situations of learning and situations of expectations, babies are in fact able to really quickly use their experience to shift the ways different areas of their brain respond to the environment," said Lauren Emberson, one of the researchers, who will join the Princeton faculty Sept. 1 as an assistant professor of psychology. She comes to Princeton from the University of Rochester, where she is a postdoctoral associate.

The research is described in the article, "Top-down modulation in the infant brain: Learning-induced expectations rapidly affect the sensory cortex at 6 months," published online June 20 in the Proceedings of the National Academy of Sciences. The other authors are John Richards of the University of South Carolina and Richard Aslin of the University of Rochester.

The researchers exposed one group of infants to a pattern that included a sound -- like a honk from a clown horn or a rattle -- followed by an image of a red cartoon smiley face. Another group saw and heard the same things, but without any pattern.

The researchers used functional near-infrared spectroscopy, a technology that measures oxygenation in regions of the brain using light, to assess brain activity as the infants were exposed to the sounds and images.

After exposing the infants to the sounds and images for a little over a minute, the researchers began omitting the image. For the infants who had been exposed to the pattern, brain activity was detected in the visual areas of the brain even when the image didn't appear as expected.

"We find that the visual areas of the infant brain respond both when they see things, which we knew, but also when they expect to see things but don't," Emberson said.

The finding could help shed light on the mysteries of neural development, the researchers said.

"Part of the reason I wanted to establish this type of phenomenon in infants is because I think it's a really good candidate mechanism for how infants are using their experiences to develop their brains," Emberson said. "There's a lot of work that shows babies do use their experiences to develop. That's sort of intuitive, especially if you're a parent, but we have no idea how the brain is actually using the experiences."

The findings offer insights that can shape future research in the area, said Janet Werker, a professor and Canada research chair in the Department of Psychology at the University of British Columbia who studies the roots of language acquisition.

"Most exciting to me is the evidence this work provides that from very early in infancy, the cortex is able to set up expectations about incoming events," said Werker, who was not involved in the research. "This shows that infants not only learn about their external worlds, but are ready -- from very early in life -- to make predictions about the co-occurrence of events on the basis of very brief previous experience. This work thus has the potential to transform future research on infant learning to focus not on just what infants can learn, but to look at learning as a more active process, focusing more on how learning begets subsequent learning."

Emberson is continuing to explore the topic by examining the phenomenon in infants who are at risk for poor developmental outcomes, specifically those who were born prematurely. She also is examining whether infants' visual expectations boost their visual abilities.

The research was primarily funded by the National Institutes of Child Health and Development.

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Study: Infant's brains develop faster than we thought

A recent study shows that infant's brains develop much more quickly than previously thought.

Scientists from the University of Louvain have discovered that a key element of infant brain development occurs years earlier than previously thought.

The way we perceive faces -- using the right hemisphere of the brain -- is unique and sets us apart from non-human primates. It was thought that this ability develops as we learn to read, but a new study published in the journal eLife shows that in babies as young as four months it is already highly evolved.

"Just as language is impaired following damage to the brain's left hemisphere, damage to the right hemisphere can impair our ability to distinguish faces so it is critical to understand how it develops," says co-author Bruno Rossion, Principal Investigator at the University of Louvain.

Researchers used a cap fitted with electrodes to monitor the brain activity of 15 babies as they sat on their mothers' laps and watched a rapid succession of images over 20 seconds. They were shown 48 images of faces that differed in viewpoint, colour, lighting, and background, interspersed with 200 images of animals, plants, and human-made objects.

Each image was shown for only 166 milliseconds, the same rate used for adult studies. Compared to other images, the appearance of a face was shown to coincide with a specific spike in stimulation of the right hemisphere of the brain. The difference between the right and the left hemisphere was even more pronounced than in the same study with adults, confounding previous assumptions.

"Given the enormous resources devoted to digital face recognition, the babies' brain accomplishment is not trivial," says Rossion. "The success of this research method in babies demonstrates that it can be used in all ages to improve our understanding of how we develop the ability to perceive complex images."

Humans far outperform computer algorithms in categorizing natural visual images. The face is such a frequent and socially important stimulus in human development that it is ideal for studying how we develop the ability to visually categorize objects.

A fundamental element of face perception is our ability to tell individuals apart. The authors can now use the same methods to define when this emerges and how it develops with age.

"Parents and carers are already aware of how quickly babies' brains develop but, until now, gathering evidence has been hard due to the limitations of the methods used," says Rossion.

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Study: Mutations causing autism are linked to brain development

A study shows that specific mutations that cause autism are linked to how the child's brain develops.

Scientists at the University of California, San Diego School of Medicine have found that mutations that cause autism in children are connected to a pathway that regulates brain development. The research, led by Lilia Iakoucheva, PhD, assistant professor in the Department of Psychiatry, is published in the February 18 issue of Neuron.

The researchers studied a set of well-known autism mutations called copy number variants or CNVs. They investigated when and where the genes were expressed during brain development. "One surprising thing that we immediately observed was that different CNVs seemed to be turned on in different developmental periods," said Iakoucheva.

Specifically, the scientists noted that one CNV located in a region of the genome known as 16p11.2, contained genes active during the late mid-fetal period. Ultimately, they identified a network of genes that showed a similar pattern of activation including KCTD13 within 16p11.2 and CUL3, a gene from a different chromosome that is also mutated in children with autism.

"The most exciting moment for us was when we realized that the proteins encoded by these genes form a complex that regulates the levels of a third protein, RhoA," said Iakoucheva. Rho proteins play critical roles in neuronal migration and brain morphogenesis at early stages of brain development. "Suddenly, everything came together and made sense."

Further experiments confirmed that CUL3 mutations disrupt interaction with KCTD13, suggesting that 16p11.2 CNV and CUL3 may act via the same RhoA pathway. RhoA levels influence head and body size in zebrafish, a model organism used by geneticists to investigate gene functions. Children with 16p11.2 CNV also have enlarged or decreased head sizes and suffer from obesity or are underweight. "Our model fits perfectly with what we observe in the patients," said Guan Ning Lin, PhD, a fellow in Iakoucheva's laboratory and co-first author with Roser Corominas, PhD.

Interestingly, the RhoA pathway has recently been implicated in a rare form of autism called Timothy syndrome, which is caused by the mutation in a completely different gene. "The fact that three different types of mutations may act via the same pathway is remarkable," said Iakoucheva. "My hope is that we would be able to target it therapeutically."

Iakoucheva and colleagues are planning to test RhoA pathway inhibitors using a stem cell model of autism. "If we can discover the precise mechanism and develop targeted treatments for a handful of children, or even for a single child with autism, I would be happy," she said.

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Why students need to get enough sleep

This article explains why it is so important for young adults, especially students, need to get enough sleep.

Humans need sleep. Young adults especially need it, and more  of it if possible. While growth spurts may be over, teenaged brains are still developing, and they will not fully mature until a person’s mid-20s, at the least. While students are in school trying to expand their minds, the very structure of their brains is expanding at the same time. Young adults need to balance academics with their sleep, which actually aids in learning and development. It may often seem like these two activities are at odds with each other, but their correlation is important.

Young adults have odd sleeping schedules, and it is not completely their fault. Developing brains of adolescents are wired to go to sleep later. When combined with heavy collegiate workloads, freedom from parental restrictions and the atmosphere of the city that never sleeps, it is no wonder that NYU students often go to sleep extremely late. While late bedtimes alone can be troubling, affecting everything from throwing off our circadian rhythms to our immune systems, this issue is compounded during the winter time. Moreover, students from warmer regions with longer days and shorter nights may not be aware of the effects the winter can have on one’s system. By going to bed late, young adults exacerbate these effects, which can lead to medical issues.

Seasonal affective disorder — a form of depression caused by changes in seasons — is among the potential complications. It can be triggered by a variety of factors, including an unnatural sleep schedule and decreased exposure to light. Symptoms of seasonal affective disorder usually manifest during fall and winter, and deficient sleep during this period can make individuals more vulnerable to depression. Research indicates that going to bed late when the sun sets later is not necessarily problematic. An 11 a.m. wake-up time gives one plenty of sunlight to maintain proper Vitamin D levels and circadian rhythm. Going to bed late when the sun goes down early is a recipe for disaster, however, because an 11 a.m. wake-up time means five hours of sunlight at the most. Students should be wary of seasonal affective disorder and take sleep seriously. Depression in the middle of a semester can jeopardize both academics and social life.

In college, personal well-being is seldom prioritized. This should not be the case — sleep is an essential tool for physical and mental health. Sleeping in late for Palladium brunch rather than waking up to an early breakfast may seem preferable, but a balanced sleep schedule can literally make winter much brighter. Suspend late-night study sessions, close Netflix and go to sleep — your mind and body will be grateful.

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Brain development in people with autism

This article discusses how brains develop in people with autism.

Geneticists at Heidelberg University Hospital's Department of Molecular Human Genetics have used a new mouse model to demonstrate the way a certain genetic mutation is linked to a type of autism in humans and affects brain development and behavior. In the brain of genetically altered mice, the protein FOXP1 is not synthesized, which is also the case for individuals with a certain form of autism. Consequently, after birth the brain structures degenerate that play a key role in perception. The mice also exhibited abnormal behavior that is typical of autism. The new mouse model now allows the molecular mechanisms in which FOXP1 plays a role to be explained and the associated changes in the brain to be better understood.

"While these kinds of results from basic research cannot be directly translated into treatment, they are still quite valuable for the affected individuals or in this case, for their parents and family. For many of them, it is important to be able to specifically put a name to the disorder and understand it. It can make dealing with it easier," said Professor Gudrun Rappold, Head of the Department of Molecular Human Genetics at Heidelberg University Hospital and senior author of the article. The results have now been published in a preliminary online version in the journal Molecular Psychiatry in cooperation with Miriam Schneider, Institute of Psychopharmacology at the Central Institute of Mental Health in Mannheim, and Dr. Corentin Le Magueresse, German Cancer Research Center (DKFZ) and Professor Hannah Monyer, Department of Clinical Neurobiology, Heidelberg University Hospital and DKFZ in Heidelberg.

Autism is a congenital perception and information-processing disorder in the brain that is frequently accompanied by intellectual disability and in rare cases, superior intelligence and special gifts such as photographic memory. The disorder is characterized by limited social interaction, repetitive behavior and language impairment. Furthermore, a wide range of other disturbances can occur. "Today, in addition to the defect in the FOXP1 gene, we are familiar with other genetic mutations that cause autism or increase the risk of this kind of disorder. However, we are only able to understand how they affect the molecular processes in the neurons, brain development and behavior for a few of these mutations," Rappold said.

This is also the case for FOXP1. Back in 2010, clear signs that structural flaws in this protein play a role in autism and mental disability had been discovered. But what role does it play in the healthy brain? What signal pathways is it involved in? Which other proteins does it interact with and exactly what damage is caused by its absence? The new mouse model has helped to shed light on these questions. The researchers discovered that the mice were born with a normally developed brain for the most part. During the course of the first weeks of life, the striatum, which is important for perception and behavior, degenerates. In a centrally located brain structure as well -- the hippocampus -- which is indispensable for developing long-term memory and recall, microscopically visible changes occur that can also impact signal processing. It could be proven, for example, that in the affected neurons the impulse conduction is changed through which signals are transmitted between neurons.

In addition to the striatum, the ventricles of the brain are degenerated; these are adjacent structures in the murine brain. "Enlarged ventricles were also detected in humans with a FOXP1 mutation," explained Dr. Claire Bacon, who works in the Molecular Human Genetics Department and is first author of the publication. The changes also trigger abnormal behavior that is comparable to the symptoms of autistic patients. The mice barely noticed their fellow mice and did not attempt to make contact to them. Further symptoms include stereotypical compulsive repetitive behaviors, hyperactivity and disturbed nestbuilding behavior.

The researchers now intend to study to what extent the communication of noise by FOXP1 mice (mice communicate via noises in the ultrasonic range) is impaired and whether there are also parallels to the disturbances in patients with FOXP1 mutation in this area as well. In addition, they plan to characterize the newly identified genes impacted by the FOXP1 in the brain and find out which signaling cascades and response paths are disrupted. In this way, they hope to find starting points for a specific treatment. "However, we first have to understand exactly how these changes occur before we can develop treatment concepts," Rappold stressed.

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Guidelines for pediatric concussion

Comprehensive guidelines for pediatric concussion are now available.

Pediatric emergency medicine researchers at the Children's Hospital of Eastern Ontario (CHEO) together with the Ontario Neurotrauma Foundation (ONF) today launch the first comprehensive pediatric concussion guidelines.

"There have been recommendations and policies on concussion available in the past, but they tend to have focused on sports-related injury and not on children and youth," said Dr. Roger Zemek, project leader, scientist at CHEO, and Assistant Professor of Pediatrics and Emergency Medicine at the University of Ottawa. "We've developed a reliable resource that is valuable for everyone affected by pediatric concussion: from children and their families, to health care providers, and to schools and recreational organizations. This is so important because children get more concussions than adults do, with increased risk because their brains are still developing."

The pediatric guidelines were initiated by ONF, managed by CHEO, and developed by an expert panel including over 30 members across Canada and the United States led by Dr. Roger Zemek. The project team included representation from the full spectrum of pediatric health disciplines (emergency medicine, family practitioners, neurologists, rehabilitation professionals, etc.) It took over 2 years to review more than 4,000 academic papers, and numerous meetings, to create the first comprehensive pediatric concussion guidelines for healthcare professionals, parents and/or caregivers, schools and/or community sports organizations.

These new guidelines provide healthcare providers with evidence-based recommendations to standardize the diagnosis and management of concussion in children aged 5 to 18 years old, from the initial assessment through to the period of recovery (which might last months.) Furthermore, it fills a need to standardize the reintegration into school and social activities, both of which are crucial to children and adolescents during their formative years.

"These are the first comprehensive pediatric guidelines that we're aware of; they reflect the very best available evidence today," said Dr. Zemek. "It was fascinating to see how recommendations have changed over time. Years ago, children were told to 'rest' after concussion, which means something entirely different today with the onset of technology -- now, rest also includes a break from screen time."

The guidelines include numerous tools and clear instructions for all levels of user. For example, the guidelines provide a pocket tool to be used by a coach or parent at the sideline to recognize concussion and offer advice on when to remove kids from play and when to seek emergent medical attention. For the emergency department physician, algorithms are provided to guide the decision whether or not to obtain CT scans, and examples of written discharge handouts for patients and families are included. For family physicians and nurse practitioners in the community, the guidelines provide recommendations for ongoing symptom management and decision tools to help navigate 'return-to-learn' and 'return-to-play'. For school boards, the guidelines provide an example of a policy statement regarding pediatric concussion.

"These guidelines are exceedingly clear and comprehensive. I think this will be an indispensable resource for caregivers in a wide range of care settings, and also be accessible for the general public," said Rebekah Mannix, MD, MPH, Assistant Professor of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.

The guidelines are free and available at http://www.onf.org/documents/guidelines-for-pediatric-concussion and http://www.concussionsontario.org/guidelines-for-pediatric-concussion

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Study shows more signs that autism begins during pregnancy

A study shows that due to the nature of brain development during pregnancy and autism, it is very likely that autism development begins while a mother is pregnant.

Children with autism show key "patches of disorganization" in the outer layers of the brain, according to a new study said to offer more evidence that the developmental disorder begins in the womb.

Experts have long believed autism involves disruptions in typical brain development, going back to pregnancy. The new study, reported online March 27 in the New England Journal of Medicine, offers more direct evidence of such early origins.

For the study, researchers examined samples of brain tissue from 22 children after death -- 11 with autism and 11 without. They were able to spot tiny patches of disrupted development dotting the outer layers of the brain in the children with autism.

Differences like that would take shape during prenatal development, said Ed Lein, a researcher at Seattle's Allen Institute for Brain Science, who worked on the study.

"This is pretty direct evidence of a prenatal origin," Lein said.

An autism researcher who reviewed the study agreed. "The foundation for this would likely be prenatal," said Dr. Walter Kaufmann, a neurologist at Boston Children's Hospital. "How early in the prenatal period? That's hard to say."

An even bigger question is, What causes the early disruptions in brain development? Lein and Kaufmann said it's impossible to pin down.

"We still need to try to understand that," Lein said.

In general, however, experts believe autism arises from genetic susceptibility and yet unknown environmental factors. "Ultimately, it's an interplay between genes and environment," Kaufmann said.

In the United States, an estimated one in 88 children has an autism spectrum disorder, which affects the ability to communicate and interact with others. Some kids are profoundly affected, speaking very little or not at all and focusing obsessively on just a few interests. Others have milder problems communicating and reading social cues, such as other people's gestures and facial expressions.

Researchers have managed to find a few hundred genes that are linked to autism risk. And although there is no definite environmental culprit, studies have tied certain factors during pregnancy to an increased risk, including exposure to high levels of air pollution, low intake of the B vitamin folate and viral infections.

For the new study, Lein and his colleagues examined small samples of the neocortex -- the outer surface of the brain. During fetal development, the neocortex forms six layers, each with its own specialized brain cells. As those cells develop, they take on a "genetic signature" that can be visualized in tissue samples, using sophisticated techniques.

Overall, the study found, brain tissue from children with autism showed tiny patches where certain genetic signatures were absent from brain cells.

What's more, those patches were concentrated in areas associated with higher order brain functions, such as understanding language and social cues.

"That makes sense," Kaufmann said. "Those are the areas where you would expect to find abnormalities."

The phenomenon, he said, was seen in 10 of the 11 autistic children, even though the severity of their symptoms varied. Some, for example, had been diagnosed with intellectual disability, while others had not.

Lein said the fact that the brain tissue showed small patches of disruption, rather than pervasive abnormalities, is "potentially good news." It suggests that much of the neocortex is actually typical in children with autism, he said.

That might help explain why autistic toddlers who get early behavioral therapy often show significant improvements, Lein said. It's possible the brain is able to "rewire," to an extent, to get around some of the trouble spots seen in this study.

In general, experts say the earlier such therapy starts, the better. The problem is, most children are not diagnosed with autism until after they reach age 4, according to the U.S. Centers for Disease Control and Prevention.

Kaufmann said researchers are working on finding objective "biomarkers," such as proteins in the blood, that could be used to detect autism earlier. But any such tests are a long way off, he said.

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Brain development disruption during pregnancy may result in autism

A study shows that autism begins during brain development during pregnancy.

Researchers at the University of California, San Diego School of Medicine and the Allen Institute for Brain Science have published a study that gives clear and direct new evidence that autism begins during pregnancy.

The study will be published in the March 27 online edition of the New England Journal of Medicine.

The researchers -- Eric Courchesne, PhD, professor of neurosciences and director of the Autism Center of Excellence at UC San Diego, Ed S. Lein, PhD, of the Allen Institute for Brain Science in Seattle, and first author Rich Stoner, PhD, of the UC San Diego Autism Center of Excellence -- analyzed 25 genes in post-mortem brain tissue of children with and without autism. These included genes that serve as biomarkers for brain cell types in different layers of the cortex, genes implicated in autism and several control genes.

"Building a baby's brain during pregnancy involves creating a cortex that contains six layers," Courchesne said. "We discovered focal patches of disrupted development of these cortical layers in the majority of children with autism." Stoner created the first three-dimensional model visualizing brain locations where patches of cortex had failed to develop the normal cell-layering pattern.

"The most surprising finding was the similar early developmental pathology across nearly all of the autistic brains, especially given the diversity of symptoms in patients with autism, as well as the extremely complex genetics behind the disorder," explained Lein.

During early brain development, each cortical layer develops its own specific types of brain cells, each with specific patterns of brain connectivity that perform unique and important roles in processing information. As a brain cell develops into a specific type in a specific layer with specific connections, it acquires a distinct genetic signature or "marker" that can be observed.

The study found that in the brains of children with autism, key genetic markers were absent in brain cells in multiple layers. "This defect," Courchesne said, "indicates that the crucial early developmental step of creating six distinct layers with specific types of brain cells -- something that begins in prenatal life -- had been disrupted."

Equally important, said the scientists, these early developmental defects were present in focal patches of cortex, suggesting the defect is not uniform throughout the cortex. The brain regions most affected by focal patches of absent gene markers were the frontal and the temporal cortex, possibly illuminating why different functional systems are impacted across individuals with the disorder.

The frontal cortex is associated with higher-order brain function, such as complex communication and comprehension of social cues. The temporal cortex is associated with language. The disruptions of frontal and temporal cortical layers seen in the study may underlie symptoms most often displayed in autistic spectrum disorders. The visual cortex -- an area of the brain associated with perception that tends to be spared in autism -- displayed no abnormalities.

"The fact that we were able to find these patches is remarkable, given that the cortex is roughly the size of the surface of a basketball, and we only examined pieces of tissue the size of a pencil eraser," said Lein. "This suggests that these abnormalities are quite pervasive across the surface of the cortex."

Data collected for the Allen Brain Atlas, as well as the BrainSpan Atlas of the Developing Human Brain was developed by a consortium of partners and funded by the National Institute of Mental Health. It allowed scientists to identify specific genes in the developing human brain that could be used as biomarkers for the different layer cell types.

Researching the origins of autism is challenging because it typically relies upon studying adult brains and attempting to extrapolate backwards. "In this case," Lein noted, "we were able to study autistic and control cases at a young age, giving us a unique insight into how autism presents in the developing brain."

"The finding that these defects occur in patches rather than across the entirety of cortex gives hope as well as insight about the nature of autism," added Courchesne.

According to the scientists, such patchy defects, as opposed to uniform cortical pathology, may help explain why many toddlers with autism show clinical improvement with early treatment and over time. The findings support the idea that in children with autism the brain can sometimes rewire connections to circumvent early focal defects, raising hope that understanding these patches may eventually open new avenues to explore how that improvement occurs.

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Brain impairment and Restless Legs Syndrome

Those who have Restless Legs Syndrome also seem to have implicated early brain development.

In a study published online in Genome Research, researchers of the Helmholtz Zentrum München und the Technische Universität München have demonstrated that a common genetic variant associated with Restless Legs Syndrome (RLS) alters the expression of a critical gene during fetal development of the brain. This leads to alterations of the developing forebrain indicating an anatomical region involved in RLS.

Restless Legs Syndrome (RLS), a neurological disorder characterized by unpleasant sensations in the legs and the urge to move them, is not caused by a single genetic defect, but rather is a complex disorder influenced by many genetic and environmental components. Previously, researchers identified genetic variants in RLS patients; however, how these variants, each of which only has a small effect, contributed to RLS was unclear.

MEIS1 gene variant leads to altered development of the brain

In this new study, authors from the Helmholtz Zentrum München (HMGU) and Technische Universität München as well as the Stanford Center for Sleep Medicine and Sciences demonstrate how one of these variants may contribute to RLS. The RLS-associated variant is located in a non-coding region of the MEIS1 gene and led to decreased ability to activate gene expression. Specifically, the authors observed the reduced gene expression in the future basal ganglia in the forebrain. "Here we have pinpointed down to an anatomical region for RLS," says lead author of the study, Prof. Juliane Winkelmann from HMGU, who is currently doing research at the Stanford University.

"The RLS-associated variant is located in an intron of MEIS1, a transcription factor involved in organ development and maintenance. The risk variant binds more strongly to the transcriptional regulator CREB1, which may lead to the reduced MEIS1 expression," explains Prof. Dr. Wolfgang Wurst from HMGU. Furthermore, screening analyses in animal models with reduced MEIS1 expression, conducted by the Institute of Experimental Genetics at the HMGU, led by Prof. Dr. Martin Hrabě de Angelis, showed hyperactivity, which resembles the human condition of RLS.

Reduced gene activity predisposition for RLS

Interestingly, the non-coding region only seems to be active during early brain development, suggesting that RLS, which is associated with aging, may have fetal origins. "Minor alterations in the developing forebrain during early embryonic development are probably leading to a predisposition to RLS," Winkelmann said. "Later in life, during aging, and together with environmental factors, these may lead to the manifestation of the disease."

In further studies researchers aim to investigate the affected cells in the forebrain. Based on their findings new treatment strategies for RLS may be developed.

This study provides one of the first in-depth examinations of a genetic variant identified in a genome-wide association study, which examines many individuals for genetic variants that are linked to a trait. Although many variants are often reported in these studies, it has been difficult understand how variants contribute to disease because they often lie in non-coding regions of the genome and have small effect sizes. This work also reveals that combinatorial use of multiple approaches will be likely required to unravel the physiological causes most of human diseases.

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Autism may be due to specific chemical switch

A study shows that autism may be caused by a specific faulty chemical switch that does not get turned on causing the brain to not develop normally.

Autism may result from a faulty chemical switch that doesn't get flipped in time to help the brain develop normally, a new research study suggests.

Building on what they hope will be an important insight into the cause of autism, French researchers are testing a high blood pressure medication on dozens of European children with autism.

The team, which has a financial stake in the drug, has tried it on 30 children with autism; now they are testing it in more, hoping to improve core characteristics of autism for the first time.

There are drugs to treat some of autism's symptoms, but none that address the underlying social and communication difficulties and repetitive behaviors, which define the condition. Previous attempts to develop an effective drug against the condition, which affects at least one in 88 U.S. schoolchildren, have either failed or are also still experimental.

In a study out today in the journal Science, the researchers offer an explanation for the promise of their drug, bumetanide, a generic diuretic long used to treat the fluid retention of high blood pressure.

The researchers found that the drug, given during pregnancy, could reverse autism symptoms in newborn mice bred with a genetic condition that often causes autism in people, and in rats exposed to the epilepsy drug valproic acid, which is known to trigger autism.

They suspect that bumetanide is flipping a chemical switch in the brain — changing the chemical GABA from stimulating electrical activity in the brain to tamping it down. This switch needs to be flipped during or near birth for the brain to develop normally, says lead researcher Yehezkel Ben-Ari of the French Institut National de la Santé et de la Recherche Médicale, in Marseilles, France.

Because this switch fails to flip in rodents with two very different triggers of autism, the researchers say they may have found an underlying cause of the condition.

That is a "pretty incredible finding and really great," says Andrew Zimmerman, a pediatric neurologist and autism expert at the University of Massachusetts Medical School in Worcester, Mass.

He and other researchers note that it's too early for people to try the drug outside of carefully watched clinical trials. There are just so many unknowns, from what the drug will do to the developing brain to how much of the drug to give and when.

"So many things cure cancer in mice and rats, and so many things cure all kinds of things and then when we give them to humans they have adverse affects and don't fix the problems we thought they could fix," says Gary Goldstein, president and CEO of the Kennedy Krieger Institute, a Baltimore-based clinic and research center. "I wouldn't give it to my child, I can tell you that."

Ben-Ari and his colleagues have patented a version of bumetanide and formed a company, Neurochlore, in Marseilles, to test the drug in children. He says bumetanide should not be given to pregnant women — despite his success with rodents — because it is impossible to determine which children will go on to develop autism and unethical to test on healthy ones.

It should be used as early in childhood as possible, Ben-Ari says, and his team is testing the drug in children as young as 2. Autism is typically diagnosed around age 4, but experts are working to push that diagnosis earlier. It is widely believed that the sooner treatment begins, the more effective it is likely to be.

Ben-Ari says he is hopeful that the drug will show benefits across a broad spectrum of children with autism, but behavioral therapy and possibly other pharmaceutical treatments will likely still be needed, too, he says.

"It's important for people to understand there is no drug to cure a medical disease as complicated as autism," he says.

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Connections within young children's brains strengthen while they sleep

A study shows that as children under five years old sleep, the connections between the left and right halves of their brain strengthen showing the importance of sleep in young children.

As young children sleep, the connections between the right and left sides of their brains strengthen, according to a small new study.

Researchers measured the brain activity of eight children while they slept at ages 2, 3 and 5 years. They found that connections in the brain generally became stronger during sleep as the children aged.

The strength of the connections between the left and right sides of the brain increase as much as 20 percent over a night's sleep, according to the study, which was published online Nov. 12 in the journal Brain Sciences.

"There are strong indications that sleep and brain maturation are closely related, but at this time, it is not known how sleep leads to changes in brain structure," study leader Salome Kurth, a postdoctoral researcher at the University of Colorado, Boulder, said in a university news release.

How sleep disruption during childhood may affect brain development and behavior will be examined in future studies.

"I believe inadequate sleep in childhood may affect the maturation of the brain related to the emergence of developmental or mood disorders," Kurth said.

It was already known that the brain changes drastically during early childhood. New connections are formed, others disappear and a fatty layer called "myelin" forms around nerve fibers in the brain. The growth of myelin strengthens the connections by speeding up the transfer of information, according to background information included in the news release.

Maturation of nerve fibers improves children's skills in areas such as language, attention and impulse control. But it hasn't been clear what role sleep plays in the development of such brain connections.

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Poverty in children and brain development - A Neuro-Thanksgiving Consideration

A Neuro-Thanksgiving Consideration

This study looks at a link between poverty during early childhood and impaired brain development. JR


Poverty in early childhood appears to be associated with smaller brain volumes measured through imaging at school age and early adolescence, according to a study published byJAMA Pediatrics, a JAMA Network publication.

Poverty is known to be associated with a higher risk of poor cognitive outcomes and school performance, according to the study background.

Joan Luby, M.D., of the Washington University School of Medicine, St. Louis, and colleagues investigated the effect of poverty on brain development by examining white and cortical gray matter, as well as hippocampus and amygdala volumes in a group of children ages 6 to 12 years who were followed since preschool. The 145 children were recruited from a larger group of children who participated in a preschool depression study.

The authors report that "exposure to poverty during early childhood is associated with smaller white mater, cortical gray matter, and hippocampal and amygdala volumes," the authors write.

Study findings also indicate that the effects of poverty on hippocampal volume were mediated (influenced) by caregiving and stressful life events.

"The finding that the effects of poverty on hippocampal development are mediated through caregiving and stressful life events further underscores the importance of high-quality early childhood caregiving, a task that can be achieved through parenting education and support, as well as through preschool programs that provide high-quality supplementary caregiving and safe haven to vulnerable young children," the study concludes. 

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Study: Exercising while pregnant can help your child's brain

A study shows that exercising while pregnant can enhance a child's brain development which can positively effect the child over a lifetime.

As little as 20 minutes of moderate exercise three times per week during pregnancy enhances the newborn child's brain development, according to researchers at the University of Montreal and its affiliated CHU Sainte-Justine children's hospital. This head-start could have an impact on the child's entire life.

"Our research indicates that exercise during pregnancy enhances the newborn child's brain development," explained Professor Dave Ellemberg, who led the study. "While animal studies have shown similar results, this is the first randomized controlled trial in humans to objectively measure the impact of exercise during pregnancy directly on the newborn's brain. We hope these results will guide public health interventions and research on brain plasticity. Most of all, we are optimistic that this will encourage women to change their health habits, given that the simple act of exercising during pregnancy could make a difference for their child's future." Ellemberg and his colleagues Professor Daniel Curnier and PhD candidate Élise Labonté-LeMoyne presented their findings today at the Neuroscience 2013 congress in San Diego.

Not so long ago, obstetricians would tell women to take it easy and rest during their pregnancy. Recently, the tides have turned and it is now commonly accepted that inactivity is actually a health concern. "While being sedentary increases the risks of suffering complications during pregnancy, being active can ease post-partum recovery, make pregnancy more comfortable and reduce the risk of obesity in the children," Curier explained. "Given that exercise has been demonstrated to be beneficial for the adult's brain, we hypothesized that it could also be beneficial for the unborn child through the mother's actions."

To verify this, starting at the beginning of their second trimester, women were randomly assigned to an exercise group or a sedentary group. Women in the exercise group had to perform at least 20 minutes of cardiovascular exercise three times per week at a moderate intensity, which should lead to at least a slight shortness of breath. Women in the sedentary group did not exercise. The brain activity of the newborns was assessed between the ages of 8 to 12 days, by means of electroencephalography, which enables the recording of the electrical activity of the brain. "We used 124 soft electrodes placed on the infant's head and waited for the child to fall asleep on his or her mother's lap. We then measured auditory memory by means of the brain's unconscious response to repeated and novel sounds," Labonté-LeMoyne said. "Our results show that the babies born from the mothers who were physically active have a more mature cerebral activation, suggesting that their brains developed more rapidly."

The researchers are now in the process of evaluating the children's cognitive, motor and language development at age 1 to verify if these differences are maintained.

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Brain Development Determines ADHD Recovery

Studies show that around 50% of children with ADHD grow out of the condition while the rest become adults with ADHD. This article claims that the pattern of a child's brain development could determine if a child grows out of their ADHD or not.

Some people grow out of their childhood attention-deficit/hyperactivity disorder (ADHD) and some don't. In fact, around 50% of individuals diagnosed as children continue to suffer from ADHD as adults.

Researchers are trying to understand the reasons why, and relatedly, whether there are any differences that distinguish the two groups. Gender, ethnicity, socioeconomic class, and symptom severity have already been ruled out as potentials. So, perhaps there is a distinguishing variable in the brain? Dr. Philip Shaw at the National Human Genome Research Institute and his colleagues conducted a study to find out.

They already knew from prior work that cortical structure is thinner in adults with ADHD, particularly in regions of the brain that play important roles in cognitive functioning and attention. However, that work was cross-sectional, meaning it was conducted at a single point in time, so any changes over time weren't captured. Thus, they focused on those same regions in this study, but conducted a longitudinal study so they could link trajectories of symptoms with trajectories of brain development, particularly the structure of cortical regions that control attention.

They recruited 92 children with ADHD, with a mean age of 11, who underwent repeated structural imaging scans and clinical assessments over the years, including as adults at a mean age of 24 years. For comparison, they also scanned 184 volunteers without ADHD.

They found that ADHD continued into adulthood in 37 (40%) of the participants diagnosed with childhood ADHD, and these individuals showed increased rates of thinning. In contrast, the cortical thickness of individuals who achieved remission of their ADHD developed toward the normal range.

"We find that differences in patterns of brain growth are linked with differences in the adult outcome of childhood ADHD. Differences in these regions -- specifically a thinner cortex -- are found in childhood ADHD," Shaw further explained. "However, for the group whose ADHD improved with age, these differences tend to resolve and by adulthood, these regions did not differ significantly from individuals who never had ADHD. By contrast, for the group with persistent ADHD, childhood differences persisted in the 'attention' regions of the brain."

These findings seem to suggest that the trajectory of cortex development differentiates people who recover from childhood ADHD from people whose disorder continues into adulthood.

"The development of the cortex seems to be a critical factor influencing the recovery from childhood ADHD. However, there is much that we do not understand about this relationship," commented Dr. John Krystal, Editor of Biological Psychiatry. "Cortical thinning may be related to the pruning of connections in the brain, in this case, connections with the prefrontal cortex. The current data would seem to suggest that excessive trimming of connections is a risk factor for the persistence of ADHD into adulthood. But we do not yet understand which connections are being trimmed, why these connections disappear, and how this loss of connections contributes to ADHD symptoms."

More work will be necessary to answer these questions, but Shaw concludes that "understanding how differences in brain development are tied to the course of ADHD is the first step in developing tools to help us predict the outcome of childhood ADHD."

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Studies claim autism begins in the womb

Studies claim that the brain changes that indicate autism is developing begin in the womb during pregnancy.

Two new studies add to a growing body of evidence pointing to pregnancy as a critical period in the brain changes that lead to autism.

One study, published Tuesday in Annals of Neurology, finds a four-fold increase in autism among women who had very low levels of a key thyroid hormone, called thyroxine. Researchers found the link in a study of more than 4,000 Dutch mothers and children. Doctors took blood samples from women around the 13th week of pregnancy, then followed up six years later, asking women to fill out a standard psychological checklist about the child's behavior and emotional traits.

A second study, published Monday in JAMA Pediatrics, notes that pregnant women who have their labor started or sped up artificially are slightly more likely to have autistic children.

The increased autism risk in the JAMA study likely stems from an underlying problem with the pregnancy, rather than any of the methods used to jump-start labor, says lead author Simon Gregory of the Duke Institute of Molecular Physiology.

It's possible that "infants destined to develop autism are less likely to send out the correct biochemical signals for normal progression of labor," says Tara Wenger, a pediatric genetics fellow at the Children's Hospital of Philadelphia, who wasn't involved in either study.

Authors of the JAMA study note their research doesn't definitively prove a link betwen labor induction and autism. They say doctors shouldn't change the way they manage labor and delivery based on their study, funded by the Environmental Protection Agency.Gustavo Roman, lead author of the thyroid research neurologist/neuroepidemiologist at Houston Methodist Hospital, says his study can't prove cause and effect, either. But proper thyroid function is crucial to many aspects of health. So he says it makes sense that women who are pregnant, or planning to become pregnant, ask doctors to check their thyroid function and urine iodine. These women also should take prenatal vitamins that contain iodine, a key element in thyroid function, Roman said in a statement.

Pregnancy complications increase the risk of many developmental disorders, says Michael Rosanoff, associate director for public health research and scientific review at Autism Speaks, an advocacy group.

And a growing number of studies now link autism to a variety of things that can compromise the health of a pregnancy, says Rosanoff, who wasn't involved in either study. Researchers are increasingly looking at prenatal risk factors for autism, because this period plays a key role in brain development.

But studies have found that children are at higher risk for autism if they are born early or very small; if they are in medical distress during delivery; if they have older mothers or fathers; or if they are born less than a year after an older sibling. Autism risk also goes up if a mother has diabetes or high blood pressure; is obese; is infected with rubella, or German measles; is exposed to significant air pollution during pregnancy; had low levels of folic acid; takes medications such as an anti-seizure drug called valproic acid; or makes antibodies toxic to the fetal brain.

Science has ruled out vaccines as a cause of autism, says Gregory, who notes that the original myth about autism and immunizations arose from bogus research that has since been retracted.

And while the link between autism and jump-starting labor is consistent with smaller, earlier studies, the research doesn't prove that labor induction or augmentation actually causes autism, Gregory says.

In Gregory's study, researchers analyzed the records of 625,042 North Carolina births, which were linked to school records that noted any diagnosis of autism.

Those records didn't specify where children fell on the autism spectrum, the study says.

Doctors can induce or speed up labor in several ways, such as by applying a hormone gel to the cervix or giving women intravenous oxytocin, an artificial version of a natural hormone involved in labor, Gregory says.

Women whose labor was induced were 13% more likely to have an autistic child, compared to women whose labor wasn't induced. Women whose labor was sped up were 16% more likely to have a child later diagnosed with autism, the study found. Those whose labor was both induced and augmented were 27% more likely to have an autistic child.

In comparison, the risk of autism went up 23% when the mother had diabetes, and 25% when the fetus was in distress, the study says.

There was no increase in autism risk among women who had C-sections, Gregory says.

Women shouldn't be afraid to have their labor induced, says JAMA study co-author Chad Grotegut, a Duke maternal-fetal medicine specialist. The risk of harm to a baby in distress is far greater than the modest risk of autism. Inducing labor can often reduce the risk of stillbirth, such as when a pregnancy lasts more than a week or so beyond the usual 40 weeks, says Grotegut. Augmenting labor, which may be done when natural labor stalls, can reduce the risk of maternal or fetal infections or postpartum hemorrhage.

But Gregory says scientists should look more closely at labor induction with oxytocin. Oxytocin, sometimes called the "love hormone," plays a key role in social behavior and reasoning.

Gregory and other researchers are investigating oxytocin to treat some of the symptoms of autism.

About one in 88 American children have an autism diagnosis, according to the Centers for Disease Control and Prevention.

Rather than one disease, autism is now regarded as a collection of conditions with similar traits but different causes, Rosanoff says. People on the autism spectrum are extremely diverse. Some are non-verbal and profoundly disabled; others have successful careers, particularly in science and technology, describing themselves as different, rather than disabled.

"Autism is so heterogeneous," Rosanoff says. "We're never going to get to the one cause."

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Scientists grow mini human brains

Scientists found a way to grow mini three-dimensional human brains in a lab. This will help in the discovery of brain development and how different disorders may develop.

Complex human brain tissue has been successfully developed in a three-dimensional culture system established in an Austrian laboratory. The method described in the current issue of Natureallows pluripotent stem cells to develop into cerebral organoids -- or "mini brains" -- that consist of several discrete brain regions.

Instead of using so-called patterning growth factors to achieve this, scientists at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences (OeAW) fine-tuned growth conditions and provided a conducive environment. As a result, intrinsic cues from the stem cells guided the development towards different interdependent brain tissues. Using the "mini brains," the scientists were also able to model the development of a human neuronal disorder and identify its origin -- opening up routes to long hoped-for model systems of the human brain.

The development of the human brain remains one of the greatest mysteries in biology. Derived from a simple tissue, it develops into the most complex natural structure known to man. Studies of the human brain's development and associated human disorders are extremely difficult, as no scientist has thus far successfully established a three-dimensional culture model of the developing brain as a whole. Now, a research group lead by Dr. Jürgen Knoblich at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) has just changed that.

Brain Size Matters

Starting with established human embryonic stem cell lines and induced pluripotent stem (iPS) cells, the group identified growth conditions that aided the differentiation of the stem cells into several brain tissues. While using media for neuronal induction and differentiation, the group was able to avoid the use of patterning growth factor conditions, which are usually applied in order to generate specific cell identities from stem cells. Dr. Knoblich explains the new method: "We modified an established approach to generate so-called neuroectoderm, a cell layer from which the nervous system derives. Fragments of this tissue were then maintained in a 3D-culture and embedded in droplets of a specific gel that provided a scaffold for complex tissue growth. In order to enhance nutrient absorption, we later transferred the gel droplets to a spinning bioreactor. Within three to four weeks defined brain regions were formed."

After only 15 -- 20 days, so-called "cerebral organoids" formed which consisted of continuous tissue (neuroepithelia) surrounding a fluid-filled cavity that was reminiscent of a cerebral ventricle. After 20 -- 30 days, defined brain regions, including a cerebral cortex, retina, meninges as well as choroid plexus, developed. After two months, the mini brains reached a maximum size, but they could survive indefinitely (currently up to 10 months) in the spinning bioreactor. Further growth, however, was not achieved, most likely due to the lack of a circulation system and hence a lack of nutrients and oxygen at the core of the mini brains.

Microcephaly in Mini Brains

The new method also offers great potential for establishing model systems for human brain disorders. Such models are urgently needed, as the commonly used animal models are of considerably lower complexity, and often do not adequately recapitulate the human disease.

Knoblich's group has now demonstrated that the mini brains offer great potential as a human model system by analysing the onset of microcephaly, a human genetic disorder in which brain size is significantly reduced. By generating iPS cells from skin tissue of a microcephaly patient, the scientists were able to grow mini brains affected by this disorder. As expected, the patient derived organoids grew to a lesser size.

Further analysis led to a surprising finding: while the neuroepithilial tissue was smaller than in mini brains unaffected by the disorder, increased neuronal outgrowth could be observed. This lead to the hypothesis that, during brain development of patients with microcephaly, the neural differentiation happens prematurely at the expense of stem and progenitor cells which would otherwise contribute to a more pronounced growth in brain size. Further experiments also revealed that a change in the direction in which the stem cells divide might be causal for the disorder.

"In addition to the potential for new insights into the development of human brain disorders, mini brains will also be of great interest to the pharmaceutical and chemical industry," explains Dr. Madeline A. Lancaster, team member and first author of the publication. "They allow for the testing of therapies against brain defects and other neuronal disorders. Furthermore, they will enable the analysis of the effects that specific chemicals have on brain development."

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