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: A mother's presence soothes infants' brains

A study shows that a mother's presence and care can make an infant's pain go away and changes the infant's brain activity.

A mother's "TLC" not only can help soothe pain in infants, but it may also impact early brain development by altering gene activity in a part of the brain involved in emotions, according to new study from NYU Langone Medical Center.

By carefully analyzing what genes were active in infant rat brains when the mother was present or not present, the NYU researchers found that several hundred genes were more, or less, active in rat infants experiencing pain than in those that were not. With their mothers present, however, fewer than 100 genes were similarly expressed.

According to senior study investigator and neurobiologist Regina Sullivan, PhD, who is scheduled to present her team's findings at the Society for Neuroscience annual meeting in Washington, D.C., on Nov. 18, the research is believed to be the first to show the short-term effects of maternal caregiving in a distressed infant pup's brain. The study was also designed to support her research into the long-term consequences of differences in how mammals, including humans, are nurtured from birth.

"Our study shows that a mother comforting her infant in pain does not just elicit a behavioral response, but also the comforting itself modifies -- for better or worse -- critical neural circuitry during early brain development," says Sullivan, a professor at the NYU School of Medicine and its affiliated Nathan S. Kline Institute for Psychiatric Research.

For the study, researchers performed genetic analyses on tissue from the almond-sized amygdala region of the infant rat pups' brains that is responsible for processing emotions, such as fear and pleasure.

Sullivan, whose earlier research showed how the mother's presence controlled electrical signaling in the infant pup's brain, says her latest findings shed insight on the complexity of treating pain in newborns.

"Nobody wants to see an infant suffer, in rats or any other species," says Sullivan. "But if opiate drugs are too dangerous to use in human infants because of their addictive properties, then the challenge remains for researchers to find alternative environmental stimuli, including maternal presence, coddling, or other cues, such as a mother's scent, that could relieve the pain."

Sullivan cautions, however, that the long-term consequences of these genetic modifications must also be compared to the short-term benefits for tying pain stimuli during infancy to such a powerful symbol of safety and security as the infant's mother.

"The more we learn about nurturing the infant brain during infancy, the better prepared we are to deal long-term with treating problems that arise from pain, and physical and mental abuse experienced during infancy," says Sullivan.

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Brain abnormalities seen in late pre-term infants

A study looked into MRI scans of late pre-term infant and found that they have brain abnormalities.

Babies born 32 to 36 weeks into gestation may have smaller brains and other brain abnormalities that could lead to long-term developmental problems, according to a new study published online in the journal Radiology.

Much of the existing knowledge on preterm birth and brain development has been drawn from studies of individuals born very preterm, or less than 32 weeks into gestation at birth.

For the new study, researchers in Australia focused on moderate and late preterm (MLPT) babies -- those born between 32 weeks, zero days, and 36 weeks, six days, into gestation. MLPT babies account for approximately 80 percent of all preterm births and are responsible for much of the rise in the rates of preterm birth over the last 20 years. Despite this, to date there have been no large-scale studies published on brain alterations associated with MLPT birth that may provide insight into brain-behavior relationships in this group of children.

"In those very preterm babies, brain injury from bleeding into the brain or a lack of blood flow, oxygen or nutrition to the brain may explain some of the abnormal brain development that occurs," said the study's lead author, Jennifer M. Walsh,M.B.B.Ch., B.A.O., M.R.C.P.I., from the Royal Women's Hospital in Melbourne, Australia. "However, in some preterm babies, there may be no obvious explanation for why their brain development appears slow compared with babies born on time."

To learn more, the researchers performed magnetic resonance imaging (MRI) exams on 199 MLPT and 50 term-born infants (greater than 37 weeks gestation) between 38 to 44 weeks of gestation. They looked for signs of brain injury and compared the size and maturation of multiple brain structures in the two groups.

While injury rates were similar between the two groups, MLPT birth was associated with smaller brain size at term-equivalent age. In addition, MLPT infants had less developed myelination in one part of the brain and more immature gyral folding compared with term-born controls. Myelination -- the formation of a fatty insulating sheath around some nerve fibers -- and gyral folding -- the folding of the cerebral cortex to increase the brain's surface area -- are important processes in early brain development.

The findings suggest that MLPT birth may disrupt the expected trajectory of brain growth that would normally occur in the last two or so months in utero, according to Dr. Walsh.

"Given that brain growth is very rapid in the last one-third of pregnancy, it is perhaps not surprising that being born during this potentially vulnerable period may disrupt brain development," she said. "Brain growth is very complex, involving not only the neurons with which we think and do things, but also the other brain cells that support the neurons and are vital for normal brain function."

The researchers are hoping to learn in greater depth the impact that moderate to late preterm birth has on the brain, so that they can then begin to try different treatments designed to improve brain function and long-term outcome in these infants.

"Medications, along with early intervention to help parents understand their baby's needs, have been effective in helping very preterm babies catch up to their term-born peers," Dr. Walsh said. "However, whether any of the existing treatments will help babies born between 32 and 36 weeks is unknown, as they have not been studied very much at all."

The researchers plan to follow the infants in the study group through childhood to learn more about the relationship between brain abnormalities and later outcomes. They also are assessing additional MRI information about brain structure and function in these children.

"Understanding what problems they have and what might be causing them is the first step in trying to improve their long-term outcome," Dr. Walsh said.

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Study: Ultrasound shows risk of autism at birth

This study claims that an ultrasound within the first few days of life can show brain abnormalities that can indicate a risk of developing autism later in life.

Low-birth-weight babies with a particular brain abnormality are at greater risk for autism, according to a new study that could provide doctors a signpost for early detection of the still poorly understood disorder.

Led by Michigan State University, the study found that low-birth-weight newborns were seven times more likely to be diagnosed with autism later in life if an ultrasound taken just after birth showed they had enlarged ventricles, cavities in the brain that store spinal fluid. The results appear in the Journal of Pediatrics.

"For many years there's been a lot of controversy about whether vaccinations or environmental factors influence the development of autism, and there's always the question of at what age a child begins to develop the disorder," said lead author Tammy Movsas, clinical assistant professor of pediatrics at MSU and medical director of the Midland County Department of Public Health.

"What this study shows us is that an ultrasound scan within the first few days of life may already be able to detect brain abnormalities that indicate a higher risk of developing autism."

Movsas and colleagues reached that conclusion by analyzing data from a cohort of 1,105 low-birth-weight infants born in the mid-1980s. The babies had cranial ultrasounds just after birth so the researchers could look for relationships between brain abnormalities in infancy and health disorders that showed up later. Participants also were screened for autism when they were 16 years old, and a subset of them had a more rigorous test at 21, which turned up 14 positive diagnoses.

Ventricular enlargement is found more often in premature babies and may indicate loss of a type of brain tissue called white matter.

"This study suggests further research is needed to better understand what it is about loss of white matter that interferes with the neurological processes that determine autism," said co-author Nigel Paneth, an MSU epidemiologist who helped organize the cohort. "This is an important clue to the underlying brain issues in autism."

Prior studies have shown an increased rate of autism in low-birth-weight and premature babies, and earlier research by Movsas and Paneth found a modest increase in symptoms among autistic children born early or late.

The study was supported by a grant from the National Institutes of Health.

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Connections in the Developing Brains of 3rd Trimester Babies

Scientists found the order and strength of brain connections in developing fetuses. This information may be used to understand how brain connections can go wrong leading to disorders such as dyslexia, ADHD, and autism.

Using real-time images of brain connections developing in late-stage fetuses, scientists say they've been able for the first time to compare the order and strength of these connections.

The research, though very preliminary, might one day lead the way to more effective therapies for brain disorders such as dyslexia, attention-deficit/hyperactivity disorder (ADHD) and autism, the researchers said.

Scientists from the U.S. National Institute of Child Health and Human Development and Wayne State University School of Medicine looked at 25 fetal brains from a group of pregnant women between 24 and 38 weeks of gestation. The researchers used an imaging technique called functional MRI (fMRI) to visualize "communication" between various regions of the brain.

The scientists learned that connections between the right and left sides of the brains got stronger as fetuses grew older. They said they also learned that shorter distances between matching areas produced stronger signals than longer spans between corresponding areas on the brain's outer edges.

"What we're seeing is a picture of emerging connectivity . . . that the right and left side are kind of building a bridge to each other," said study author Moriah Thomason, an assistant professor of pediatrics at Wayne State, in Detroit. "It's evidence for the fact that already in fetal life, this anatomy is being constructed in a way that we would expect. But for the first time, we can show the development of these networks."

The findings are published in the Feb. 20 issue of the journal Science Translational Medicine.

While scientists had previously used fMRI scans on fetuses, this new research is the first to compare a group of fetuses and identify features of development, Thomason said. Nearly 90 percent of the pregnant mothers participating in the study were black, while the rest were white or multiracial. They later delivered 17 boys and eight girls.

MRI scans don't emit radiation, thus minimizing risk to the fetuses during the procedure. The technique showed significant connections between half of the dozens of brain areas tested.

The findings might provide groundwork for understanding how and when brain development may go awry during gestation, Thomason said. This may possibly lead to better understanding of conditions such as ADHD, dyslexia and autism, which are thought to arise from disrupted brain networks, she said.

"If we know what gets in the way of those [normal] processes, we have a better shot at treating those disorders," Thomason said. "It's not just about early identification. An additional valuable outcome is, when you can see what normal looks like and see what disruption looks like, you have the opportunity to pick out patterns that tell you about the origin of that disease," she explained.

"The brain can be a tattletale to what is going on in those diseases," Thomason added, "and that can help us develop novel treatments."

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Infant brain's blood flow is regulated differently than an adult brain

Researchers found the blood flow in a developing infant's brain is not the same as an adult's brain. This has many implications for treating developmental disorders.

A new study by Columbia Engineering researchers finds that the infant brain does not control its blood flow in the same way as the adult brain. The paper, which the scientists say could change the way researchers study brain development in infants and children, is published in the February 18 Early Online edition ofProceedings of the National Academy of Sciences (PNAS).

"The control of blood flow in the brain is very important" says Elizabeth Hillman, associate professor of Biomedical Engineering and of Radiology, who led the research study in her Laboratory for Functional Optical Imaging at Columbia. "Not only are regionally specific increases in blood flow necessary for normal brain function, but these blood-flow increases form the basis of signals measured in fMRI, a critical imaging tool used widely in adults and children to assess brain function. Many prior fMRI studies have overlooked the possibility that the infant brain controls blood flow differently."

"Our results are fascinating" says Mariel Kozberg, a neurobiology MD-PhD candidate who works under Hillman and is the lead author of the PNAS paper. "We found that the immature brain does not generate localized blood-flow increases in response to stimuli. By tracking changes in blood-flow control with increasing age, we observed the brain gradually developing its ability to increase local blood flow and, by adulthood, generate a large blood-flow response."

The study results suggest that fMRI experiments in infants and children should be carefully designed to ensure that maturation of blood-flow control can be delineated from changes in neuronal development. "On the other hand," says Hillman, "our findings also suggest that vascular development may be an important new factor to consider in normal and abnormal brain development, so our findings could represent new markers of normal and abnormal brain development that could potentially be related to a range of neurological or even psychological conditions."

Functional magnetic resonance imaging, or fMRI, is one of several brain-imaging methods that measure changes in blood flow to detect the presence and location of neuronal activity. In adults, blood-flow increases occur in specific regions of the brain during a particular task like moving your hand or reacting to a stimulus. FMRI relies upon measuring decreases in deoxygenated hemoglobin resulting from this blood-flow increase to understand which parts of the brain are responsible for different actions and emotions. FMRI and other brain-imaging methods are currently being widely used to explore brain development, and to understand disorders in infants and children including autism and ADHD.

"Until now, we had been studying blood flow in the adult brain," Hillman notes, "but we became interested in several studies that reported odd, sometimes negative, blood-flow responses in newborn and premature infants and decided to carefully explore what was different about the immature brain compared to the adult. Initially, I saw these studies as a way to watch how the adult system assembled itself during development. Then we realized how important our findings were to those using brain imaging to study child development and developmental disorders."

The team used a unique multispectral optical intrinsic signal imaging system (MS-OISI) built in Hillman's lab to perform the research. MS-OISI is a high-speed, high-resolution imaging approach that takes advantage of the different absorption spectra of deoxygenated and oxygenated hemoglobin in order to determine changes in the concentrations of each. The researchers found that, with increasing age, there was a gradual development of a localized increase in blood flow, while a strong, delayed decrease in flow was consistently present. Only by adulthood was the positive increase able to balance the decrease in flow.

"Our results suggest that the infant brain might not be able to generate localized blood- flow increases, even if there is neuronal activity occurring, and that the development of blood- flow control occurs in parallel with early neuronal development," says Kozberg. "This could suggest that fMRI studies of infants and children may be detecting changes in both vascular and neuronal development -- in fact, vascular development may be an important new factor to consider in normal and abnormal brain development."

The team also found that the younger age groups were highly sensitive to blood pressure increases in response to stimulation and that these increases can cause large increases in blood flow across the brain. "This finding indicates that the newborn brain is also unable to regulate its overall blood-flow levels," Kozberg explains. "This could explain earlier fMRI results in infants and children that were sometimes positive and sometimes negative, because it is difficult to tell whether blood pressure increases are occurring in infants and children. This result suggests that great care should be taken in setting stimulus thresholds in young subjects."

The researchers add that, since the newborn brain appears to be able to sustain itself without tightly controlled blood flow, their findings suggest that the infant brain may be intrinsically more resistant to damage due to a lack of oxygen than the adult brain. "This could be an important property to understand, both in terms of understanding how best to treat blood-flow problems in the newborn infant brain, which can cause lifelong problems such as cerebral palsy, and to potentially better understand how to treat the adult brain in conditions such as stroke," Hillman observes.

"Our lab operates at the intersection of neuroscience and engineering," continues Hillman." Not only do we develop the imaging systems that let us investigate the living brain in new ways, but like all engineers, we're fascinated with figuring out 'how things work,' and the brain is no exception."

Next steps for Hillman and her team include further defining the cellular mechanisms underlying the developing hemodynamic response at a cellular and microvascular level, using methods such as high-speed and multi-plane in-vivo two-photon microscopy, another technique developed in the lab. They're particularly interested in tracking changes in neuronal activity, microvascular architecture and connectivity, and the distribution and activity of other cellular populations thought to be associated with neurovascular coupling as a function of development.

"This will help us understand how the neonatal brain is different, and better understand how mature blood-flow control mechanisms in the adult brain work," says Kozberg. Adds Hillman, "We are also keen to take this research into the clinic and explore whether our findings could improve diagnosis and monitoring of newborn infants. Our findings so far feel like just the tip of the iceberg. There is so much more for us to do now to understand why the infant brain is so different, and how we can use our findings to improve understanding of a wealth of devastating childhood and developmental conditions."

This research was supported by grants and student fellowships from the National Institute of Neurological Disorders and Stroke, the National Eye Institute, the National Science Foundation, the National Defense Science and Engineering Graduate Fellowship, the Medical Scientist Training Program, and the Human Frontier Science Program. Hillman is also a member of the Columbia University graduate program in Neurobiology and Behavior and the Kavli Institute for Brain Sciences.

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Study: Early Autism Intervention Improves Brain Responses to Social Cues

A study shows promising signs that behavioral intervention can positively change brain function in toddlers with autism.

An autism intervention program that emphasizes social interactions and is designed for children as young as 12 months has been found to improve cognitive skills and brain responses to faces, considered a building block for social skills. The researchers say that the study, which was completed at the University of Washington, is the first to demonstrate that an intensive behavioral intervention can change brain function in toddlers with autism spectrum disorders.

"So much of a toddler's learning involves social interaction, and early intervention that promotes attention to people and social cues may pay dividends in promoting the normal development of the brain and behavior," said Geraldine Dawson, lead author and chief science officer for the advocacy group Autism Speaks.

"For the first time, parents and practitioners have evidence that early intervention can result in an improved course of both brain and behavioral development in young children," she said.

Dawson began the study while she was the director of the UW Autism Center. The study was published online Oct. 26 in the Journal of the American Academy of Child & Adolescent Psychiatry.

Forty-eight children, aged 18 to 30 months and diagnosed with autism, either participated in routine community-based interventions or the Early Start Denver Model, which emphasizes interpersonal exchanges and shared participation in activities. The model was developed by Dawson and co-author Sally Rogers, a professor at the UC Davis MIND Institute.

Participants received one of the interventions for about 20 hours each week over a period of two years. For the children randomly assigned to the ESDM group, treatment took place two hours, twice a day, five days a week, by trained interventionists who came to the child's home. The children got an extra boost from their parents, who were trained to use ESDM strategies during routine exchanges with their child.

A previous study found that the ESDM intervention improved IQ, language, and adaptive skills and the researchers wanted to know if the approach also led to brain changes.

After two years of treatment, the brain function of the participants -- now about four to five years old -- was measured with electroencephalography while the youngsters viewed social stimuli, such as faces, and nonsocial stimuli, such as toys.

"Humans are experts at processing faces, but the brains of children with autism have delays in the ability respond to faces," said co-author Sara Webb, a UW research associate professor. If the brain can quickly identify a face, she said, then it can build on this to also quickly decide whether the face is of a man or a woman, happy or sad, and familiar or not.

Children in both intervention groups showed similar brain responses to faces as did children in a control group who did not have autism, suggesting that "the high level of intervention in both groups allowed the children with autism to catch up to the children in the control group," Webb said. "That's fantastic news."

Looking at a higher level of brain processing, the researchers studied whether the treatments changed brain measures of attention and cognitive engagement when seeing faces compared with a nonsocial stimulus. Eleven of 15 -- or 73 percent -- of children in the ESDM group showed greater attention to faces than to toys. In contrast, the EEGs of only five of the 14 recipients of the community intervention, or 36 percent, showed similar activation.

"The ESDM intervention resulted in greater attention and cognition brain activity to social stimuli, and these brain function patterns are more similar to the typical developing group of children," Webb said.

She stressed not only the importance of receiving intensive early intervention for autism, but that the intervention should focus on enhancing social attention, reciprocal interactions and engagement with a social partner.

Other study authors at UW are Emily Jones, Kaitlin Venema, Rachel Lowy, Susan Faja, Dana Kamara, Michale Murias, Jessica Greenson, Jamie Winter and Milani Smith, as well as Kristen Merkle of Vanderbilt University.

The study was funded by a grant from the National Institute of Mental Health and an Autism Speaks postdoctoral fellowship awarded to Jones.

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Study: Preemies from Low-Income Families at High Risk for Dangerous Brain Bleeds

A study from Johns Hopkins shows that premies who are born to a low socioeconomic family are more likely to have dangerous hemorrhages.

While interesting, I never know how to apply this data in the office, the NICU or my cerebral palsy clinics.... JR

Babies born prematurely to low-income parents have a disproportionately high risk for developing dangerous brain bleeds that require multiple surgeries and extensive follow-up, according to a small Johns Hopkins Children's Center study.

The findings -- published online Sept. 28 in the journal Pediatric Neurosurgery and based on an analysis of 38 patients referred to Johns Hopkins for treatment of brain hemorrhages related to premature birth -- offer a sobering reminder of the role socio-economic factors can play in health outcomes, the researchers say.

The link between poverty and premature birth has been well-documented, the investigators say, but the new findings go a step further and focus on the consequences of one particularly dire and fairly common complication of prematurity -- brain hemorrhages.

"Our study shows just how detrimental and far-reaching the effects of prematurity can be, medically and otherwise, highlighting the critical need to better identify high-risk pregnancies and reduce the number of premature births," says Edward Ahn, M.D., pediatric neurosurgeon and senior author on the research.

"Brain hemorrhages can have a lifelong impact on a child's neurological and cognitive development, but also create a financial burden on the families, many of whom in our study were already economically challenged," Ahn adds.

The premature brain's blood vessels are highly vulnerable to rapid changes in blood and brain pressure that occur around birth. While some brain bleeds are small and contained within the blood vessel, others can spread further and significantly damage the brain, particularly if not diagnosed and treated promptly. Serious hemorrhages require surgery, intensive follow-up and, often, long-term care to deal with the neurological and developmental after-effects of the condition.

The study tracked 38 babies treated at Hopkins Children's between 2007 and 2010 for complications of brain hemorrhages they had suffered during preterm birth. Most infants in the study (65 percent) were from low-income families and received public health insurance(63 percent). Household income is not part of a standard medical record, but the researchers used zip code and Medicaid status as proxies for income. Medicaid is the public health insurance program for low-income children.

In addition to the higher risk for brain bleeds, the study showed babies from lower-income homes and those with public health insurance had fewer scheduled follow-up appointments and more emergency room visits, compared with babies with private health insurance and with those from higher income homes. The researchers note the differences were clear, even though they didn't reach statistical significance due to the small number of patients in the study.

"If a family foregoes a scheduled follow-up and instead ends up in the ER with a serious, yet likely preventable complication, the medical and financial consequences can be far worse not only for the family but for the health care system as a whole because ER care is more expensive than routine check-ups," Ahn says.

The investigators said their findings need to be replicated on a wider scale in order to further tease out the reasons behind the disproportionate risk.

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Cause of Common Childhood Tumors Identified

New mutation identified that could help focus treatments for common pediatric brain tumors.

Researchers at the Stanford University School of Medicine and Lucile Packard Children's Hospital have identified several gene mutations responsible for the most common childhood brain tumor, called medulloblastoma, adding evidence to the theory that the diagnosis is a group of genetically distinct cancers with different prognoses. These and accompanying findings are likely to lead to less-toxic, better-targeted treatment approaches over the next two years, the researchers said.

"We tend to treat all medulloblastomas as one disease without taking into account how heterogeneous the tumors are at the molecular level," said Yoon-Jae Cho, MD, an assistant professor of neurology and neurological sciences at Stanford, a pediatric neurologist at Packard Children's and the senior author of the new research. "This paper represents a finer-grained view of the genetic landscape of these tumors and provides us with some leads on how to develop new therapies."

The research, which appeared online in Nature July 22, is part of a large, ongoing effort to characterize genetic errors in medulloblastoma. Two companion studies on which Cho is a co-author will be published simultaneously with his paper. The three papers came from a consortium that involves scientists at Stanford, Packard Children's, the Broad Institute, Children's Hospital Boston, the Dana-Farber Cancer Institute, the German Cancer Research Center, Brandeis University and the Hospital for Sick Children in Toronto.

Current treatment for medulloblastoma, which originates in the cerebellum and affects about 250 U.S. children each year, begins with surgery to remove as much of the tumor as possible. Patients then receive a combination of radiation and chemotherapy, but the treatments are not tailored to the tumor's genetic characteristics.

Cho's team extracted DNA from 92 medulloblastoma tumors and compared it with DNA from matched blood samples from the same patients, uncovering 12 significant "point mutations" -- single-letter errors in the genetic code -- that occurred frequently in the brain cancer. A handful of the mutations had been previously identified in smaller studies of medulloblastoma, but several mutations were novel in both medulloblastoma and in cancer.

Among the newly identified mutations was one in an RNA helicase gene, DDX3X, which Cho said is the second-most common mutation in medulloblastoma tumors. "Mutations in this gene have now also been identified in other tumor types, such as chronic lymphocytic leukemia, and head and neck tumors," he said.

However, the researchers found that it was rare for the same gene mutated in several different patients' tumors. More commonly, mutations involving a set of genes regulating a single biological pathway were found in the tumors -- a pattern that is emerging across cancer genome sequencing efforts.

Though no single tumor in the study carried all 12 mutations, the researchers were able to categorize the tumors according to which mutations they possessed. "We now understand that there are certain tumors with particular genetic signatures that are really resistant to standard treatments," Cho said. Children with medulloblastoma do not routinely have their tumors' genetic signatures characterized, but Cho believes that such characterization coupled with targeted therapies could greatly enhance tumor treatment.

About two-thirds of medulloblastoma patients now survive five years past diagnosis, but many survivors suffer lasting physical or intellectual side effects from their cancer treatments. Drugs tailored to a tumor's genetic profile have the potential to save more patients while reducing side effects, Cho said.

Several of the mutations discovered affect cellular signals that switch large groups of genes on and off. "The dysregulation of these 'epigenetic programs' is becoming a common theme not only in medulloblastoma but across cancer," Cho said. Such pathways may be good targets for cancer drugs; indeed, drugs targeting one such pathway (histone methyltransferases) are currently in pre-clinical development, while agents against another pathway (Hedgehog signaling pathway) are entering phase-2 clinical trials for medulloblastoma.

Cho is the co-chair of a committee within the Pediatric Brain Tumor Consortium that guides which drugs should be moved into clinical trials next. "Our plan is that within the next one to two years we will be able to offer kids a new set of compounds that have a clear biological rationale based on our genomic studies." Cho said. "We want to make sure we're being careful of what we move forward with, but at the same time, for some of these kids we don't have many, if any, effective and durable treatment options."

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Brain Scan Can Detect Early Signs of Autism in Infants

A new study shows significant differences in brain development in high-risk infants who develop autism starting as early as age 6 months. The findings published in the American Journal of Psychiatry reveal that this abnormal brain development may be detected before the appearance of autism symptoms in an infant's first year of life. Autism is typically diagnosed around the age of 2 or 3.

The study offers new clues for early diagnosis, which is key, as research suggests that the symptoms of autism -- problems with communication, social interaction and behavior -- can improve with early intervention. "For the first time, we have an encouraging finding that enables the possibility of developing autism risk biomarkers prior to the appearance of symptoms, and in advance of our current ability to diagnose autism," says co-investigator Dr. Alan Evans at the Montreal Neurological Institute and Hospital -- the Neuro, McGill University, which is the Data Coordinating Centre for the study.

"Infancy is a time when the brain is being organized and connections are developing rapidly," says Dr. Evans. "Our international research team was able to detect differences in the wiring by six months of age in those children who went on to develop autism. The difference between high-risk infants that developed autism and those that did not was specifically in white matter tract development -- fibre pathways that connect brain regions." The study followed 92 infants from 6 months to age 2. All were considered at high-risk for autism, as they had older siblings with the developmental disorder. Each infant had a special type of MRI scan, known as diffusion tensor imaging, at 6 months and a behavioral assessment at 24 months. The majority also had additional scans at either or both 12 and 24 months.

At 24 months, 30% of infants in the study were diagnosed with autism. White matter tract development for 12 of the 15 tracts examined differed significantly between the infants that developed autism and those who did not. Researchers evaluated fractional anisotropy (FA), a measure of white matter organization based on the movement of water through tissue. Differences in FA values were greatest at 6 and 24 months. Early in the study, infants who developed autism showed elevated FA values along these tracts, which decreased over time, so that by 24 months autistic infants had lower FA values than infants without autism.

The study characterizes the dynamic age-related brain and behavior changes underlying autism -- vital for developing tools to aid autistic children and their families. This is the latest finding from the on-going Infant Brain Imaging Study (IBIS), which is funded by the National Institutes of Health (NIH) and brings together the expertise of a network of researchers from institutes across North America. The IBIS study is headquartered at the University of North Carolina, and The Neuro is the Data Coordinating Centre where all IBIS data is centralized.

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Just What's Inside Those Breasts?

Just What's Inside Those Breasts?

May 16, 2012

When writer Florence Williams was nursing her
second child, she read a research study about
toxins found in human breast milk. She decided
to test her own breast milk and shipped a
sample to a lab in Germany. What came back surprised her.

Trace amounts of pesticides, dioxin and a jet
fuel ingredient — as well as high to average
levels of flame retardants — were all found in
her breast milk. How could something like this
happen?

"It turns out that our breasts are almost like
sponges, the way they can soak up some of these chemicals, especially the ones that are fat­
loving — the ones [that] tend to accumulate in fat tissue," Williams tells Fresh Air's Terry Gross.
"Unfortunately, the breast is also masterful at converting these molecules into food in the way of
breast milk."

Learning that breasts soak up lots of chemicals made Williams wonder just what else was going on
with breasts. A lot, as it turns out. In her new book, Breasts: A Natural and Unnatural History,
Williams offers her take on — among other things — why breasts are getting bigger and
developing earlier, why tumors seem to gravitate toward the breast, and how toxins from the
environment may be affecting hormones and breast development.

She says many of those toxins, including the flame retardants found in her breast milk, may come
from ordinary household items like couches and electronics, which often contain flame retardants.
Some animal studies have shown that certain types of flame retardants interact with hormone...

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Study Claims Migraines More Likely for People With Celiac Disease

Note that the opposite is not necessarily true. I would not advocate screening every headache patient for celiac disease. JR

Migraine headaches are more likely to plague people with celiac disease than those without it, according to new research.

The connection between the digestive tract and the brain has been studied in Europe, but this is the first time American researchers have linked celiac disease and other bowel problems with migraines, said study co-author Dr. Alexandra Dimitrova.

"We found significantly higher prevalence of headaches in patients with celiac disease compared to those without it," said Dimitrova, a neurology resident at the Neurological Institute at Columbia University Medical Center in New York City.

Celiac disease is an autoimmune disease that affects one out of every 133 people in the United States, according to the Celiac Disease Foundation. People with the condition can't eat pizza, pastries and other foods that contain wheat gluten. Symptoms include stomach problems, joint pain and headaches.

Neurologic manifestations of celiac disease have been described since the 1960s, and poor coordination and subtle sensory loss are among the symptoms commonly reported, Dimitrova said.

The researchers also looked at two other related conditions. More than 1.5 million Americans have Crohn's disease or ulcerative colitis, the most common forms of inflammatory bowel disease, according to the Mayo Clinic. Both conditions inflame the lining of the intestines and can cause bouts of diarrhea, rectal bleeding and abdominal cramps, as well as pain, fever and weight loss.

For the study, Dimitrova and her colleagues surveyed more than 700 people using a four-page questionnaire. A detailed medical history was logged, which included whether a participant had been diagnosed with celiac disease or inflammatory bowel disease, or had problems eating foods containing wheat. Researchers also asked about headache history. Lifestyle details -- such as smoking, alcohol and coffee habits -- also were documented.

"We ended up analyzing 502 people," Dimitrova said. "We eliminated those who had head trauma or brain tumors, everybody who drank more than two alcoholic beverages a day and people who drank four or more cups of coffee a day -- anything that could be headache contributors."

The yearlong study found that 188 people had celiac disease, 111 had inflammatory bowel disease and 25 were gluten-sensitive -- meaning they had not tested positive for celiac disease but reported symptoms when they ate foods with wheat. The other 178 healthy individuals served as the control group.

Chronic headaches of any kind were reported by 56 percent of gluten-sensitive participants, 30 percent of those with celiac disease and 23 percent of those with inflammatory bowel disease, while only 14 percent of the control group reported headaches.

Dimitrova said that when the researchers screened specifically for migraines, 21 percent of those in the celiac group and 14 percent of the inflammatory bowel disease group met the criteria for the sometimes disabling headaches, compared with only 6 percent of the control group.

"Our findings suggest that migraine is a common neurologic manifestation in celiac disease, gluten sensitivity and [inflammatory bowel disease]," said Dimitrova, who also said they don't know what the mechanism is.

"It's possible the patients with [inflammatory bowel disease] have a generalized inflammatory response, and this may be similar in celiac disease patients, where the whole body, including the brain, is affected by inflammation," she said. "The other possibility is that there are antibodies in celiac disease that may ... attack the brain cells and membranes covering the nervous system and somehow cause headaches. What we know for sure is that there is a higher prevalence of headache of any kind, including migraine headaches, compared to healthy controls."

Dr. Alessio Fasano, medical director of the University of Maryland Center for Celiac Research in Baltimore, said it is not unusual to hear his patients with celiac disease complain of headaches.

"Roughly one-third of celiac disease or gluten-sensitive patients we see have some form of migraine," Fasano said. "That link with gluten-related disorders is very well known to us. We don't know why. What is the connection?"

Dimitrova said many patients reported major improvements in the frequency and severity of headaches once they adopted a gluten-free diet.

Fasano said he has seen it work the other way around, too, in that people with migraines often also complain of belly woes and some experience less digestive trouble when they go on gluten-free diets.

"One thing is for sure: Many people with migraines, when they go on a gluten-free diet, the migraines improve or go away," he said.

Migraine sufferers who don't get relief from treatments should ask their doctors about a celiac disease screening, Dimitrova said.

The researchers presented their findings last week at the American Academy of Neurology annual meeting in New Orleans. The data and conclusions should be viewed as preliminary until published in a peer-reviewed journal.

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Study: MRI sheds light on cognitive risks for very preterm infants

White matter injury on term MRI of very preterm-born infants is predictive of future cognitive impairment, according to a study published in the May issue of Pediatrics. This discovery further supports the benefit of obtaining term MRI for very preterm-born infants, according to the authors.

“Because ultrasound scans are insensitive to most MRI findings, early MRI may help identify a group of very preterm born infants with an increased risk of later cognitive impairment,” wrote Osuke Iwata, MD, of the department of paediatrics and child health at Kurume University School of Medicine in Kurume, Japan, and colleagues. “Such information may provide an important key to improve follow-up strategies and to allow better risk stratification for future clinical trials which enroll very preterm born infants.”

While previous studies have demonstrated associations between white matter injury and cognitive impairment in very preterm-born children, this study is the first longitudinal study comparing term MRI findings, based on an MRI completed at term age, with outcomes at nine years old, according to the authors.

Seventy-six very preterm-born infants were imaged as part of the prospective study. Neurodevelopmental outcomes were assessed at 9 years old in 60 subjects using the Wechsler Intelligence Scale for Children, which tests different IQ indices.

Overall, mildly low intelligence scores (less than 85) were observed in 23.3 percent of the study cohort for verbal IQ, 41.7 percent for performance IQ and 30 percent for full-scale IQ. Moderately low scores (less than 70) were observed in 3.3 percent for verbal IQ and 11.7 percent for both performance IQ and full-scale IQ. Cerebral palsy was diagnosed in 10 percent of the children and 56.7 percent required special assistance at school.

Abnormal white matter appearances on the term MRI were predictive of mildly and moderately low performance and full-scale IQ scores, as well as cerebral palsy and the need for special assistance at school. It was also predictive of mildly low verbal IQs, but not moderately low verbal scores. Abnormal gray matter appearances did not predict any of the outcome measures.

“In very preterm born children, reduced cortical gray matter volume has also been associated with poor cognitive outcome at school age. In our current study, abnormal gray matter appearances at term were associated with the presence of white matter injury but not with any of the outcome measures at nine years old,” wrote Sachiko Iwata, MD, and colleagues. They explained that cortical gray matter lesions may contribute less to later cognitive functioning because neurologic functioning associated with gray matter injury may be affected more by other factors, such as education and family environment.

The authors concluded that term MRI may be able to help screen preterm-born infants and aid in earlier diagnosis of cognitive impairment.

“Additional studies with longer follow-up periods are still required, because neurodevelopmental assessments performed at early childhood period may not reflect cognitive functioning at school age and thereafter, either because of the limited reliability of early assessment tools or because cognitive function itself may significantly alter under the influence of numerous intrinsic/extrinsic factors such as plasticity, compensation, reorganization of injured brain, environment, and education.”

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Maternal Obesity May Influence Brain Development of Premature Infants

Obesity is a modifiable risk factor that can affect cognition. JR

Maternal Obesity May Influence Brain Development of Premature Infants

ScienceDaily (Mar. 8, 2012) — Maternal obesity may contribute to cognitive impairment in extremely premature babies, according to a new study by researchers at Wake Forest Baptist Medical Center.

"Although in the past decade medical advances have improved the survival rate of babies born at less than seven months, they are still at very high risk for mental developmental delays compared with full-term infants," said Jennifer Helderman, M.D., assistant professor of pediatrics at Wake Forest Baptist and lead author of the study. "This study shows that obesity doesn't just affect the mother's health, but might also affect the development of the baby."

Published in the March issue of the journal Pediatrics, the study looked at 921 infants born before 28 weeks of gestation during 2002 to 2004 at 14 participating institutions. The researchers assessed the babies' placenta for infection and other abnormalities, interviewed the mothers and reviewed their medical records. At age 2, the children's cognitive skills were evaluated using the Mental Development Index (MDI) portion of the Bayley Scales of Infant Development, a commonly used measure.

The scientists found that both maternal obesity and lack of high school education were associated with impaired early cognitive function, as was pre-term thrombosis (blood clot) in the placenta.
"We weren't really surprised by the socioeconomic factors because it has been repeatedly shown that social disadvantage predicts worse infant outcomes," Helderman said. "However, obesity is of particular interest because it is becoming more prevalent and it is potentially modifiable during the pre-conception period and pregnancy."

Obesity has been linked to inflammation, and inflammation can damage the developing brain, Helderman said. What isn't known is if the obesity-related inflammation in the mother is transmitted to the fetus.
"Few studies have addressed prenatal risk factors of cognitive impairment for infants born this prematurely. The long-term goal is to use information from studies like ours to develop treatments that prevent cognitive impairment in extremely premature babies," Helderman said.
Helderman's colleague, Michael O'Shea, M.D., section head of neonatology at Wake Forest Baptist, is currently conducting a study that follows these same babies into mid-childhood to determine long-term cognitive problems.

More than 30,000 extremely premature babies are born each year in the United States.