Early Brain Development Research

Jenny Prater, contact 

About Us 

The Early Brain Development Program is a collaboration for the comprehensive study of early brain development. Our group combines pediatric neuroimaging with genetic, environmental, and behavioral methodologies to study brain development in healthy children and those at risk for developing neuropsychiatric disorders. The goal of our research is to aid in the understanding of how the healthy brain develops and how deviations from normal development can lead to a diseased state.    


Funding Sources

National Institues of Child Health and Human Development 
Early Brain Development in 1 and 2 Year Olds (R01)

National Institues of Mental Health
Early Brain Development in Twins (R01)
Genome Wide Identification of Variants Affecting Early Human Brain Development (RO1)
Gut Microbiota and Anxiety: A Mechanistic Study of Human Infants (R21/R33)
White Matter and Working Memory Development in Typical and High-Risk Children (KO1)


Current Studies

Early Brain Development in 1 and 2 Year Olds
PI: Dr. John Gilmore

The first years of life are the most dynamic and perhaps the most critical phase of postnatal brain development. Abnormalities in early childhood brain development have been implicated in neurodevelopmental disorders, including autism and schizophrenia, though very little is known about this crucial time period. This project focuses on the continued study of a cohort of typically developing children using innovative image analysis tools.  Our previous studies have found rapid gray matter development and white matter maturation in the first 2 years of life, with marked regional differences in the cortex and in white matter tracts, consistent with temporal patterns of sensory/motor and higher integrative function development. We also found significant relationships between white matter maturation and working memory. These findings indicate that neonatal brain structure, reflective of prenatal brain development and the rapid growth trajectories of the first two years of life, likely play an important role in longer trm outcome. In our current study we will extend follow-up of our cohort to 6 years of age and focus on structure/function relationships and the predictive value of early brain structure for later childhood brain structure and cognitive function. We are collecting diffusion tensor imaging,  at ages 1, 2, 4, and 6 years and assessing cognitive development, including general cognitive function and working memory. Developmental trajectories of cortical gray matter (including cortical thickness and surface area) and white matter (including tract-based spatial statistics and quantitative tractography) will also be studied. New knowledge gained in this study will provide a framework for understanding abnormalities of early childhood brain development in neurodevelopmental disorders such as autism and schizophrenia and will provide the fundamental information critical for developing preventative strategies for these disorders. 

Early Brain Development in Twins
PI: Dr. John Gilmore

Twin studies have been critical in determining the contributions of genetic and environmental factors to normal brain structure and for understanding abnormalities of brain development that underlie neurodevelopmental and neuropsychiatric disorders. In adults and older children, twin studies indicate that genes play a significant role in the variability of global brain volumes, including total brain, total gray and total white matter volumes. Other than this current study, there have been no studies of twin brain development in early childhood, the period of brain development implicated in the pathogenesis of many psychiatric disorders. In our previous studies containing over 100 twin pairs, we used prenatal ultrasound and neonatal MRI to study discordance of early brain development, and to determine genetic and environmental contributions to neonatal brain structure. We found that discordance of prenatal brain size in MZ twins is similar to that in DZ twins, but that by 1 month after birth, discordance of overall brain volume in MZ twins is already less than in DZ twins. We also found that global tissue volumes are highly heritable, similar to that observed in older children and adults, though gray matter heritability may is somewhat less. Interestingly, while global white matter volumes are highly heritable, diffusion tensor properties of specific white matter tracts are not. In our current study, we will continue enlarging this unique cohort and follow them through age 6 years with structural MRI, diffusion tensor imaging (DTI), and developmental assessments to determine how genetic and environmental factors contribute to brain development in the first years of life.

Genome-Wide Identification of Variants Affecting Early Human Brain Development 
PI: Dr. Rebecca Knickmeyer 

Recent studies strongly suggest that there are common, genetically determined pathways to risk for psychiatric and neurodevelopmental disorders including autism, intellectual disability, attention deficit disorder, and schizophrenia, but no study has investigated the relationship between genetic variation and human brain development prior to the age at which clinical symptoms are first recognized. The primary objective of the current study is to use cutting-edge techniques in genomics to identify common and rare genetic variants which impact brain development in the early postnatal period, an extremely dynamic time which may be critical in the etiology of neurodevelopmental disorders. Intracranial volume (ICV), total white matter, total gray matter, lateral ventricle volume, and maturation of white matter tracts are heritable in neonates. The project will test several major genetic mechanisms which could explain this high heritability. This study will primarily focus on the neonatal period, but participants are also returning for follow-up scans and detailed developmental assessments at 1, 2, 4 and 6 yrs of age as part of our other studies. Thus, ultimately, the information generated in this grant can be used to study genetic determinates of the trajectories of structural and functional brain development across the critical transitional period of infancy and early childhood. This is an unprecedented opportunity to identify genetic variants which impact brain development, potentially mediating risk for psychiatric and neurodevelopmental disorders. A better understanding of such genetic mechanisms has the potential to inspire new approaches to prevention, diagnosis, and treatment which are urgently needed.

Gut Microbiota and Anxiety: A Mechanistic Study of Human Infants 
PI: Dr. Rebecca Knickmeyer 

Studies in rodents show that the gut microbiome influences neurodevelopment and subsequent anxiety-related behaviors which are relevant to a wide range of psychiatric illnesses. However, there is a fundamental gap in translating animal data into the clinic: no study has directly tested whether differences in microbial colonization impact anxiety-related behavior in humans. Furthermore, the mechanisms and pathways by which microbiota alter brain development are poorly understood. Our long-term goal is to determine how colonization of the gut microbiome impacts human brain development and later risk for psychiatric illness. The objective of this project is to determine how microbial colonization impacts anxious behavior at 1 year of age and to identify signaling mechanisms and neural circuits mediating this relationship using high resolution magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and resting state fMRI (rfcMRI). This study is innovative in that it will be the first to test if and how microbial compositin relates to anxious behavior in a human cohort. This research is significant in that it is an essential first-step in developing novel interventions to promote a healthy microbiome and reduce risk for psychiatric illness.
 

White Matter and Working Memory Development in Typical and High-Risk Children
PI: Dr. Sarah J. Short 

This study is focused on characterizing the development of white matter and working memory in children who are typically developing and in children who are at genetic high-risk for schizophrenia from 1 to 8 years of age. As part of this project, we will be conducting a pilot study with typical children to determine the feasibility of measuring experience-dependent structural plasticity in white matter, following training with a standardized adaptive working memory program. This program of training and research will improve current understanding of early brain development in typical and high-risk children in relation to an early emerging and formative cognitive skill, working memory. Results from this research will be used to identify early biomarkers of risk, which can be used to inform the design of targeted preventive intervention strategies for high-risk children. Our study will help identify white matter connections that are important for the development of working memory and will determine whether they are altered in children at risk for schizophrenia. In addition, the feasibility study of working memory training in typical children will provide valuable information about the capacity to measure experience-dependent structural changes in white matter tracts. Strengthening neural networks associated with early foundational cognitive processes may help to ameliorate later impairments in other cognitive, social and developmental capacities that depend on working memory. 


People

Our lab consists of clinicians, scientists, students, and specialists from a variety of backgrounds who collaborate to investigate novel research questions with inventive approaches. 

Training

We offer training opportunities for undergraduate, graduate, and medical students as well as postdoctoral fellows. For information on how to join our lab, please contact the PI(s) you are interested in working with via email.

Special Information for Graduate Students

For any students interested in working with our lab during their Ph.D. training, Dr. Gilmore and Dr. Knickmeyer have appointments with the Neurobiology Curriculum, a Ph.D. training program that admits it's students through the larger Biological and Biomedical Science Program at UNC.

We are currently seeking undergraduate students to assist with ongoing projects and for graduate students to join our lab.


Participate

Our participants are the key to our research. Participating in research studies helps further our knowledge and understanding of how the brain develops, allowing us to identify critical time points for later treatments and interventions. There are also direct benefits to being part of our studies, including the acquisition of brain images that are reviewed by clinicians as well as cognitive assessments that evaluate behavioral development. If you are interested in participating, please visit the Recruitment page for details on our ongoing studies. 

Recruitment

Gut Microbiota and Anxiety
Principle Investigator: Dr. Rebecca Knickmeyer

The purpose of this research is to understand how microbes (tiny organisms) living in our gut affect brain development and infant behavior. We are especially interested in how babies respond to new people and situations. Babies who are fearful of new situations may be at risk for later psychiatric problems such as depression or anxiety and this could be the result of differences in their gut microbes. By participating in our study you and your child may help us better understand and prevent psychiatric problems in future generations.  

Study Summary:

Children will receive a MRI scan of the brain at 2 weeks of age. We will also collect a small sample of blood via heel prick and several samples of saliva (spit). When your child is 1 year old, we will observe how he/she responds to new people and toys. The child will then receive another MRI at this visit, along with blood and spit samples as before. We will also ask that parents collect a small fecal (stool) sample from your child prior of both visits. 

Along with your child having a thorough evaluation of brain development and early behavior, participants will receive $200 for each study visit (Potential $400 total). You will also be reimbursed for travel expenses/gas and parking. 

This is a voluntary study and all information gathered during the study is confidential. MRI has been approved by the FDA and does not use x-rays or radiation. Children will be scanned during normal sleep, so no medication or sedation is required. Heel prick will be done by trained personnel with supplies designed to minimize discomfort. 

If you are interested in participating in this study, please contact Jennifer Prater, Study Coordinator, at 919-843-5904 or 866-849-0541 (toll free) or email: .

Please note, babies cannot be in the study if they were born prematurely or transferred to a neonatal intensive care unit, weighed less than 2500 grams at births, or received antibiotics in the first 2 weeks. In addition, babies cannot participate if their mother received antibiotics during the last 3 months of pregnancy. 

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White Matter and Working Memory Development
Principle Investigator: Dr. Sarah J. Short

The purpose of this research is to study early human brain development and to determine if improving working memory capacity via cognitive training induces measurable changes in the structure of the brain. This information can also tell us about which brain regions are important for working memory early in development.

Study Summary:

Typically developing children currently enrolled in Dr. John Gilmore’s studies of early brain development who have completed their 6-year-old visit are eligible to participate in the working memory training program. This study involves a standardized 5-week cognitive training program designed to improve working memory capacity. Follow-up MRI structural scan and cognitive assessments are also collected to evaluate the impact of cognitive training compared to developmental changes that occur prior to the start of training. A follow-up visit, 6 months after training, includes cognitive assessments and parental questionnaires to assess long-term benefits of the working memory training program.

Participants will receive $25 for each component of the first visit (potential total of $50 for MRI and cognitive testing) and $75 for each component of the second visit (potential total of $150 for MRI and cognitive testing). Each child will receive a small toy/gift each week for 5 weeks as a reward for completing the cognitive training program. Transportation expenses will be reimbursed according to UNC standards. 

This is a voluntary study, no medications or sedation are involved, and the MRIs do not use radiation or x-ray. All information gathered about you and your child is strictly confidential.



If you are interested in participating in this study, please contact Dianne Evans, Study Coordinator 919-843-2389 or 866-849-0541 (toll free) or email: 
.

Please note, children identified in Dr. Gilmore’s study as being of genetic high-risk (based on maternal medical illness (HIV+, schizophrenia, major depression, bipolar disorder, etc.) or having any known chromosomal or major cogngenital abnormalities are not eligible for this current study. 

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Gut Microbiota and Brain Development in One Year Old Healthy Infants
Principle Investigator: Dr. Rebecca Knickmeyer 

This study explores the relationship between intestinal bacteria and brain development in healthy human infants at age one. MRI scans will be obtained in conjunction with fecal samples. Samples will be collected by a parent or guardian  using a custom prepared collection kit. All participants will receive a $10 check for taking part in this study upon receipt of the collected sample. 

Study Summary:

Typically developing children currently enrolled in Dr. John Gilmore’s studies of early brain development who have completed their 6-year-old visit are eligible to participate in the working memory training program.

This is a voluntary study, no medications or sedation are involved, and the MRIs do not use radiation or x-ray. All information gathered about you and your child is strictly confidential.



If you are interested in participating in this study, please contact Dianne Evans, Study Coordinator 919-843-2389 or 866-849-0541 (toll free) or email: 

Please note, children identified in Dr. Gilmore’s study as being of genetic high-risk (based on maternal medical illness (HIV+, schizophrenia, major depression, bipolar disorder, etc.) or having any known chromosomal or major cogngenital abnormalities are not eligible for this current study.


Contact

For questions about participating in our ongoing studies, please contact:

Dianne Evans, MA
Study Program Director
(919) 843-2389
866-849-9541 (toll free)
email: 

For questions concerning our research, please contact: 

John Gilmore, MD
Principal Investigator
Director of the Early Brain Development Group
(919) 445-0209
email: john_gilmore@med.unc.edu