Premature Babies Have Weaker Brain Connectivity

Megan Brooks

October 19, 2015

CHICAGO — Altered connectivity in the developing brain may underlie neuropsychiatric disorders and motor impairment associated with preterm birth, two new studies suggest.

One study shows that babies born prematurely have weaker structural and functional connections between brain regions linked to attention, communication, and emotional processing; this might help explain their increased risk for disorders, such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).

The other study suggests that motor impairments associated with preterm birth may stem from altered brain connectivity detectable before birth.

These findings "illustrate how the brain's structural and functional architecture is exquisitely sensitive to conditions before birth and how alterations to brain circuitry can set the scene for future neurologic impairment long before it arises," said Jay N. Giedd, MD, director of child and adolescent psychiatry at University of California San Diego, who moderated a press briefing October 18 at which the studies were discussed. "These new discoveries could one day help lessen the burden of early-life neurologic abnormalities."

The results were presented here at the Society for Neuroscience 2015 Annual Meeting (SfN).

Key Brain Networks Affected

Premature birth is an early life stressor that affects one in nine infants in the United States. Premature birth is associated with altered cerebral gray matter and white matter development and with developmental deficits and increased rates of psychopathology, including ASD, ADHD, and anxiety disorders.

Dr Cynthia Rogers

To get a better picture of the developmental consequences of preterm birth, Cynthia Rogers, MD, from Washington University School of Medicine, St Louis, Missouri, and colleagues used resting-state functional MRI (fMRI) and diffusion tensor imaging (DTI) to compare the brains of 58 babies born full term (>37 weeks gestational age) with those of 76 infants born very preterm (<30 weeks gestational age) but without significant brain injury. Term infants were imaged on the second or third day of life, while preterm infants were imaged close to their due date.

Compared with term infants, preterm infants had significant structural alterations in white matter tracts on DTI. "The preterm infants had either underdeveloped or immature white matter compared to the full-term infants," Dr Rogers explained.

Brain scans from babies born full term and at least 10 weeks prematurely show less coordinated activity (red and yellow areas) among premature babies. Courtesy of Washington University

"While this was widespread throughout the brain, we were really interested to see that tracts that we know connect areas that are involved in attention and emotional networks were heavily involved and affected in preterm children," she noted.

On fMRI, preterm infants also showed weaker functional connections, most notably in the default mode network (P = .001), "one of the main social and emotional networks," and the frontoparietal network (P < .001), "one of the main attention networks," Dr Rogers said. "These networks have been shown to be abnormal in children with ADHD and autism, leading us to wonder if this is indeed why preterm infants are at greater risk for these disorders."

Going forward, the researchers will try to directly relate these neonatal imaging findings to psychiatric symptoms by assessing the children at preschool and school-age. They'll also do repeat brain imaging to see whether and how the connections that were abnormal at birth have changed as the children have aged.

Roots of Motor Impairment

The other study suggests that the roots of motor impairments in preterm babies can be traced to alterations in brain connectivity present before birth.

Moriah Thomason, PhD, from Wayne State University, Detroit, Michigan, and colleagues studied pregnant women, some of whom were at high risk for preterm delivery but who were otherwise having normal pregnancies. They used resting-state fMRI to measure fetal brain function in utero in 18 fetuses born before 37 weeks and 18 born at term.

They found that term-born fetuses had higher levels of functional connectivity in "budding" motor areas of the brain compared with fetuses born preterm, suggesting that these areas are already more developed in term-born fetuses, Dr Thomason said.

The differences between term-born and preterm-born fetuses were greatest in distant brain regions, indicating that the preterm brain may have "delayed development of distant connections," she explained at the briefing; this delayed development could underlie the motor deficits seen in preterm babies. These data "support the idea that the biology of the preterm brain is different even before birth" and suggest the possibility of intervening prenatally, she said.

"Identifying alterations in neural networks before birth will provide a greater understanding of preterm brain development, leading to new ways to prevent and treat irregular neural connections that, in many infants, accompany prematurity," Dr Thomason added in a conference statement.

Dr Giedd, whose own research focuses on brain development and maturation as they relate to health and illness, noted that "for a long time people have appreciated that early interventions can have the greatest impact."

This research supports that "early intervention is the key" and represents some of the "best work going on in this field and it has enormous potential for improving the lives of youth and their families."

These studies, Dr Giedd added, highlight the importance of "connecting within the brain and connecting across time."

For years, neuroscience was about looking for "the hole" in the brain and that "kind of led nowhere. Now it's all about connectivity. How are things connected? That's been the biggest change in the last several years [and] is a fresh take on this. The trouble is, we don't yet know how to change brain connections very well. Can we do it with video games, exercise, meditation, yoga, diet? What actually tweaks these circuits for good or ill? That's for the next decade, but measuring these connections is a start. It's exciting times," Dr Giedd said.

The study by Dr Rogers and colleagues was supported by the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute of Child Health and Human Development, the McDonnell Center for Systems Neuroscience, the Child Neurology Foundation, the Cerebral Palsy International Research Foundation, and the Dana Foundation. The study by Dr Thomason and colleagues was supported by the Perinatology Research Branch of the National Institute of Child Health and Human Development and the National Institute of Environmental Health Sciences. Neither study team has disclosed any relevant financial relationships.

Society for Neuroscience 2015 Annual Meeting (SfN). Abstracts 349.08 and 252.01. Presented October 18, 2015.

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