In the world of neurodevelopment, one thing is clear: the earlier the better. Childhood is a critical time in brain development, and neuroscientists are increasingly identifying factors that can negatively affect cognition and factors that can improve cognition early in life. At the annual meeting of the Cognitive Neuroscience Society (CNS), researchers from the University of Minnesota present new work on two early interventions: one on the potential use of engineered gut microbes for infants exposed to antibiotics and the other on a choline supplement for treatment. Infants exposed before birth to alcohol.
“These conversations underscore how patient-based neuroscience can advance the field of newborn and infant care, and provide evidence-based interventions to improve cognition,” says Natalie Maitre of Nationwide Children’s Hospital, who chairs the CNS symposium on the brain of newborns and infants. “It also shows the interdisciplinary nature of this field, bringing together doctors with the latest in neuroimaging techniques, as well as other specialized fields such as microbiology.”
A microbial approach to infant health
“As a pediatrician specializing in the care of sick newborns, I have always been interested in how early exposure in life affects related long-term health outcomes,” says Dr. Sherrill Gill of the University of Minnesota. Thus her team set out to combine microbial genomic analyzes, biological computational approaches, and functional brain assessment for a better understanding of neurodevelopment in very young infants.
At CNS, Jill will present new research showing that infants with different combinations of gut bacteria process auditory and visual stimuli differently during memory tasks. “These results increase the possibility that gut bacteria are involved in developing brain function,” she says.
The study was published online at Pediatric research Led by Mary Hickey, it compares the brain activity of babies who were given antibiotics to those who weren’t in their first month of life. The researchers used an electroencephalogram (EEG) to record a type of electrical activity called event-related potentials (ERPs) in the babies’ brains in response to their mother’s voice or the voice of a stranger – a type of memory called “recognition memory” that can be evaluated in pre-articulation. Infants before any behavioral changes appear.
“Recognition memory is one of the oldest types of explicit memory that has arisen, and it is known to depend on the structures of the medial temporal lobe, including the hippocampus, which is the area of the brain affected by the disruption of the microbiome in animal models,” Gill explains. In fact, previous research on the connection between the gut and the brain has been almost exclusive in animal models, which makes this human study particularly valuable and unique. At the same time, ERP technology has been used extensively in other research to successfully predict a range of behaviors, such as later language development, reading ability, and autism risk.
ERP measurements of infants exposed to antibiotics indicated an abnormal response to their mothers’ voices compared to infants not exposed to antibiotics. All babies were healthy, and the researchers worked to control other variables, such as inflammatory responses and the infant’s gestational age.
While the new study showed an association between early antibiotic exposure and brain function in participants, researchers have not yet identified a causal relationship. “We don’t know yet if there is a specific cause and effect relationship between microbes and brain function in infants,” Gill says, “but we hope future research will be able to shed light on this.”
The work raises the possibility of creating engineering microbes as an intervention to help people early in life. “Childhood is a critical window of time for brain development, where therapeutic interventions can have impacts on the life course,” says Gill.
Damage reversal attachment
Despite decades of research showing the harmful effects of alcohol consumption during pregnancy, fetal alcohol syndrome remains common worldwide – affecting nearly 8 in 1,000 people in the general population, according to a 2017 study in Gamma Pediatrics. This syndrome causes children to have structural brain abnormalities and cognitive impairment, among other harmful effects.
Geoff Wozniak recalls encountering his first clinical case of fetal alcohol spectrum disorder early in his career, realizing for the first time that “this group was too unique, poorly understood, and had very high needs”. He also realized that there was a lack of imaging studies in this population. “So I became interested in using some of the tools that we had here at the University of Minnesota to do high-quality imaging of brain structure and function in this population that hasn’t been studied to find out something about how the brain changes through prenatal alcohol exposure in the early stages of development.”
Through this work, he and his colleagues identified a number of ways in which prenatal alcohol exposure leads to brain cell loss and disruption of important growth processes, including gene expression. For example, he says, alcohol may interfere with genes involved in myelogenesis throughout the brain.
This research included work on a possible treatment, specifically early intervention with the addition of the nutrient choline. Over a decade of a randomized, double-blind, placebo-controlled study, they saw how postpartum choline supplementation at ages 2 to 5 with prenatal alcohol exposure translated into cognitive benefits compared to those without the supplement.
In the central nervous system, he will present the findings of the participants, after four years of taking choline supplements and without other interventions since then. Those who received choline early in life showed higher nonverbal intelligence, higher visual spatial skills, higher capacity for working memory, better verbal memory, and fewer behavioral symptoms of attention deficit hyperactivity disorder (ADHD) compared to those in the placebo group.
“The more you step back in and intervene, the more leverage you have to change the developmental attire of that particular child,” Wozniak says. “So this was the exciting thing about taking these kids back and looking at their growth and seeing the significant effects of choline versus placebo on cognitive functions like working memory and even behavioral differences in terms of ADHD.”
The relationship between nutrients and brain development is not new; For example, folic acid has long been established as a supplement that prevents neural tube disorders. However, longitudinal studies examining the effects of a dietary intervention on cognition over time are relatively new, indicating an exciting convergence between cognitive neuroscience and children’s health.
Wozniak sees this work as the beginning of a potential paradigm shift in treating a range of neurodevelopmental pathways and disorders. “Our interventions are small steps but really important little steps because they show us and others that we shouldn’t think of these cases as fixed injuries that occurred before birth and that this is the end of the story,” he says. “Instead, we must learn what developmental processes have gone awry and then go back as soon as possible in treating these children, identifying them and treating them in a way that improves the rest of the neurological development.”
The seminar “Studying the Newborn and Infant Brain: From Neuroscience to Invention” will take place at 2 pm on Sunday 14 March 2021 as part of CNS 2021 Virtual, from March 13-16.
The central nervous system is committed to developing mind and brain research aimed at investigating the psychological, computational, and neurological foundations of perception. Since its founding in 1994, the association has been dedicated to bringing its 2,000 members worldwide to the very latest in research to facilitate public, professional and scholarly discourse.