Does exposure to stress early in life affect a baby’s brain development, and is there a way to single out babies who might benefit from early intervention? A two-center study led by Boston Children’s Hospital, published today in JAMA Pediatrics, used brain EEGs to begin to get at these questions in an objectively measurable way. It found that infants whose mothers reported high levels of stress have a distinct pattern of brain activity as measured by EEG — at only 2 months of age.
“The EEG has been found to be exquisitely sensitive to perturbations in the environment, and thus we are not entirely surprised to see an association between stress in a mother’s life and her infant’s brain activity,” says Charles Nelson, PhD, director of the Laboratories of Cognitive Neuroscience at Boston Children’s Hospital and the study’s senior investigator. “What we were surprised by, in part, was how early in life we see this association.”
A handful of families from around the world with a rare brain malformation called polymicrogyria have led scientists to discover a new gene that helps us speak and swallow.
The gene, SCN3A, is turned “on” primarily during fetal brain development. When it’s mutated, a language area of the brain known as the perisylvian cortex develops multiple abnormally small folds, appearing bumpy. People with polymicrogyria in this region often have impaired oral motor development, including difficulties with swallowing, tongue movement and articulating words — especially if the polymicrogyria affects both sides of the brain.
The new study, published today in Neuron, ties together human genetics, measurements of electrical currents generated by neurons, studies of ferrets and more to start to connect the dots between SCN3A, the brain malformation and the oral motor impairment. …
In 2012, researchers in the Boston Children’s Hospital lab of Christopher Walsh, MD, PhD, reported a study of three unrelated families that had children with microcephaly. All had smaller-than-normal brains — both the cerebrum and the cerebellum were reduced in size— and all had mutations that knocked out the function of a gene called CHMP1A.
It was clear that CHMP1A is needed for the brain to grow to its proper dimensions. But the study stopped there.
“Then I came along, and my goal was to figure out what this gene is doing in brain during development, and why, when you lose it, you have a small brain,” says Michael Coulter, MD, PhD, who joined the Walsh lab as a student in 2012. …
Mouse brains are tiny and smooth. Ferret brains are larger and convoluted. And ferrets, members of the weasel family, could provide the missing link in understanding how we humans acquired our big brains.
Children with microcephaly, whose brains are abnormally small, have a part in the story too. Microcephaly is notorious for its link to the Zika virus, but it can also be caused by mutations in various genes. Some of these genes have been shown to be essential for growth of the cerebral cortex, the part of our brain that handles higher-order thinking.
“I’m trained as a neurologist, and study kids with developmental brain diseases,” said Walsh in a press release from the Howard Hughes Medical Institute, which gave him a boost to his usual budget to support this work. “I never thought I’d be peering into the evolutionary history of humankind.” …
Babies’ brains are like sponges — highly tuned to incoming sensory information and readily rewiring their circuits. But when so-called critical periods close, our brains lose much of this plasticity. Classic experiments reveal this in the visual system: when kittens and mice had one eye covered shortly after birth, that eye was blind for life, even after the covering was removed. The brain never learned to interpret the visual inputs.
In 2010, a study led by Takao Hensch, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, showed that levels of a protein called Lynx1 rise just as the critical period for visual acuity closes. When the researchers deleted the Lynx1 gene in mice, the critical period reopened and mice recovered vision in the blind eye.
Radiologists who can tune in to the nuances of brain scans in children are a pretty rarified group. Only about 3 percent of U.S. radiologists, some 800 to 900 physicians, practice in pediatrics. Those specifically trained in pediatric neuroradiology are even scarcer.
To a less trained eye, normal developmental changes in a child’s brain may be misinterpreted as abnormal on MRI. Conversely, a complex brain disorder can sometimes appear normal. That’s especially true when the abnormality affects both sides of the brain equally (see sidebar).
It can be hard to find the cause of a child’s developmental delay without a proper read. “Pediatric brain scans of children under age 4 can be particularly tricky to read because the brain is rapidly developing during this period,” says Sanjay Prabhu, MBBS, a pediatric neuroradiologist at Boston Children’s Hospital. “If you’re looking at adult scans all the time, it’s incredibly difficult to transition to pediatric scans and understand what is considered ‘normal’ and ‘abnormal.’ Clinicians often wonder, ‘Should I repeat the scan? Should I send the patient to a specialist?’” …
As organs go, the brain seems to harbor an abundance of somatic mutations — genetic variants that arise after conception and affect only some of our neurons. In a recent study in Science, researchers found about 1,500 variants in each of neurons they sampled.
New research revealing the propensity of DNA to break in certain spots backs up the idea of a genetically diverse brain. Reported in Cell last month, it also suggests a new avenue for thinking about brain development, brain tumors and neurodevelopmental/psychiatric diseases. …
When we were developing in the womb, we were immersed in amniotic fluid. As our nervous systems formed, some of this fluid was trapped inside the neural tube, forming the cerebrospinal fluid that bathes our brains.
In the past, these fluids have been seen as a “cushion” or a place to dump waste products. But new research suggests that they actively participate in nervous system development.
Publishing this week in Developmental Cell, researchers led by Maria Lehtinen, PhD, and Kevin Chau in the Department of Pathology at Boston Children’s Hospital show that amniotic fluid and cerebrospinal fluid (CSF) contain rich portfolios of proteins that tell neural stem cells what to do — how to divide and what kinds of cells to make. They also show that the messages change in different phases of development. …
First in a two-part series on circadian biology and disease. Read part 2.
It’s long been known that a master clock in the hypothalamus, deep in the center of our brain, governs our bodily functions on a 24-hour cycle. It keeps time through the oscillatory activity of timekeeper molecules, much of which is controlled by a gene fittingly named Clock.
It’s also been known that the timekeeper molecules and their regulators live outside this master clock, but what exactly they do there remains mysterious. A new study reveals one surprising function: they appear to regulate the timing of brain plasticity—the ability of the brain to learn from and change in response to experiences.
“We found that a cell-intrinsic Clock may control the normal trajectory of brain development,” says Takao Hensch, PhD, a professor in the Departments of Molecular and Cellular Biology and Neurology at Harvard University and a member of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital. …
The sad experience of abandoned children in Romanian orphanages continues to provide stark lessons about the effects of neglect and deprivation of social and emotional interactions. The long-running Bucharest Early Intervention Project (BEIP) has been able to transfer some of these institutionalized children, selected at random, into quality foster care homes—and documented the benefits.
In a review article in the January 29 Lancet, BEIP investigator Charles A. Nelson, PhD, and medical student Anna Berens, MsC, both of Boston Children’s Hospital, make a strong case for global deinstitutionalization—as early in a child’s life as possible. Currently, it’s estimated that at least 8 million children worldwide are growing up in institutional settings.
The BEIP studies have documented a series of problems in institutionalized children, especially those who aren’t placed in foster care or are placed when they are older: …