April 2016

Study Maps Early Connectivity Networks in Newborn Babies’ Brains

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For parents-to-be, the third trimester of pregnancy is often a period of rapid preparation to welcome a new life into the world. Their babies are busy, too: From growing lungs that can breathe on their own, to developing neurological connections they need to feel, move, and cry, they spend those critical weeks making important preparations for life outside the womb.

Scientists are beginning to glimpse exactly how a gestating infant’s developing brain forms important connections during this period. These discoveries show the earliest scenes yet in the story of how healthy brains develop as children grow up.

“We found that brain regions are developing heterogeneously,” said Hao Huang, PhD, an investigator in radiology at The Children’s Hospital of Philadelphia and research associate professor at the Perelman School of Medicine at the University of Pennsylvania, who leads this research. “In certain periods, some brain regions develop at faster rates. Although it’s heterogeneous, it’s not random. There is a well controlled, organized pattern at work.”

Dr. Huang found that pattern places priority on early, efficient connectivity within the primary sensorimotor cortex. This prepares a baby to handle the basic needs of sensation and movement after birth.

Dr. Huang’s recent study published in the journal Cerebral Cortex mapped the functional connectivity in brains of 40 newborn infants, based on resting-state functional magnetic resonance imaging scans. He and colleagues compared the brain connectivity patterns present in babies born at various preterm ages, beginning as early as 31 postmenstrual weeks, to those born at more mature gestational ages up to full-term, or 42 postmenstrual weeks. By mapping which types of functional connectivity were present in which stages of development, they have filled an important knowledge gap about when the brain becomes organized.

Among these infants, even the youngest preterm babies’ brains had a characteristic called “small worldness” in their entire brain connectivity, a feature of networks that offer easy navigation from one area to another. In these babies’ brains, the networks through which electrical impulses can travel are analogous to well-designed road systems in a city or region. They have a useful combination of major highways interconnected with smaller side roads, so that there is always an efficient path to get from one location to another, even if there is no single direct road connecting them. If the brain networks were random or undeveloped, they would only offer the equivalent of sporadically linked side streets, making movement from one location to another slow and inefficient, riddled with meandering turns and occasional dead ends.

In addition to finding this efficient “small worldness” quality present early on in infants’ brain development, Dr. Huang and colleagues found that as gestational age increased, so did a quality called rich club structure. In rich club structure, nodes of densely connected regions make signaling more efficient within areas of the brain.

Such studies of brain connectivity in children fit into a larger context of related research that has received major investments in recent years, including President Obama’s BRAIN Initiative and the Human Connectome Project (HCP). The HCP is an ambitious NIH-funded effort to build maps of how neurons are interconnected with one another within adults’ brains, to visualize the metaphorical smaller side roads and major highways. Dr. Huang’s studies of developing brains complement the HCP, and are akin to discovering the city planners’ processes. Which roads are built first, and to what degree and in what way is the process organized?

By mapping the typical development process, Dr. Huang hopes in the future to identify biomarkers of atypical connectivity that may occur in various conditions, ranging from autism spectrum disorder to cerebral palsy. If these brain indicators can allow earlier identification of these conditions, children could potentially begin early intervention services sooner and grow up with fewer impairments related to their condition.

“We think this is a normal reference that can be used to detect certain abnormal connectivity development during this specific age period,” Dr. Huang said. “Our entire goal is to study not only this age range, but all the way from birth to adolescence.”

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