Current CNBD Research Studies
Below is a list of current CNBD research studies. Subject tags will link you to study listings by topic.
Perturbation: Substance Use, Nutrition, Genetic/Congenital/Developmental Condition, Prematurity, Social/Emotional Development, Behavioral Development, Cognitive Development, Institutional Neglect/Deprivation
Choline supplementation as a neurodevelopmental intervention in fetal alcohol spectrum disorders
Jeffrey R. Wozniak, Ph.D., L.P. (Department of Psychiatry)
Michael K. Georgieff, M.D. (Department of Pediatrics), Stephanie Carlson, Ph.D. (Institute of Child Development)
Recent data indicate that 2-5% of the U.S. population has Fetal Alcohol Spectrum Disorder (FASD) – a set of physical anomalies and neurodevelopmental deficits caused by prenatal alcohol exposure (May, Fiorentino et al. 2011). Despite the profound public health burden posed by FASD, there have been very few treatment studies of any sort in this population and no clinical trials that have attempted to directly address the neurodevelopmental deficits that are so debilitating for these individuals. There is, however, a promising line of translational research that suggests a potential role for micronutrient interventions. At the top of the list is choline, an essential nutrient for humans that is critical for normal brain development during gestation and early childhood. Although the human body produces choline, the demand cannot be met entirely endogenously and thus, some choline must be consumed in food. Extensive pre-clinical work has provided evidence that choline supplementation is effective in attenuating the neurodevelopmental deficits caused by prenatal alcohol exposure in animal models (Thomas, Biane et al. 2007, Ryan, Williams et al. 2008). Our group has taken the initial steps toward translating this work to humans. We first conducted a two-year pilot study to ensure the feasibility, tolerability, and safety of choline supplementation in 20 children with FASD (Wozniak, Fuglestad et al. 2013). Next, we completed a three-year pilot study of 40 additional children with the goals of establishing a target dosage for young children and testing efficacy in the domain of memory (Wozniak, Fuglestad et al. under review). Together, data from these two studies demonstrate that choline supplementation in 2-3 year old children with FASD improves explicit memory – a core function that is essential for normal cognitive development. Based on the time periods in which choline is effective in pre-clinical models of FASD and on the fact that the first years of human life represent a period of intense brain development, choline supplementation in young children appears to have significant potential as an intervention for neurodevelopmental disorders including FASD.
Dyadic coordination of self-regulation and social engagement in infants and caregivers
Daniel Berry, PhD (Institute of Child Development)
Isabella Stallworthy, doctoral candidate (Institute of Child Development)
The ability to contingently and dynamically engage with others is critical for human functioning throughout life. In the first year, infants’ abilities evolve from simple social orienting to engaging in complex social interactions. This progression is foundational for their emerging social, self-regulatory, and learning abilities, and is driven in part by the developmental interplay of sensitive caregiving and infants’ nascent physiological reactivity systems. In infancy, when cortical control of behavior is immature, parasympathetic control of the heart is critical for infants’ abilities to regulate their internal states and engage with others (Bazhenova & Porges, 1997). Respiratory sinus arrhythmia (RSA), a measure of heart rate variability, indexes parasympathetic control of cardiac activity by the vagus nerve.
This study aims to examine: (1) how real-time changes in infants’ RSA relate to changes in infants’ social visual attention during a) social interaction and b) a naturalistic disruption to the interaction; (2) the extent to which infants’ social visual attention and RSA are coupled in time and relate to affect, within each infant; (3) how caregivers’ RSA coordinates with infants’ RSA; as well as (4) developmental changes in these associations over the first year of life.
Effects of single-session transcranial direct current stimulation in children with cerebral palsy
Bernadette Gillick, PhD, MSPT, PT (Department of Rehabilitative Medicine)
Neurorehabilitation in cases of hemiparesis has primarily focused on intensive motor training to encourage use of the affected extremities in an effort to produce use-dependent neuroplasticity in the brain. Such interventions are effective, but require a burdensome amount of time, 60-90 hours per week, for both the child and therapist. Furthermore, some children do not respond at all to such training.
Neuromodulation is a relatively new field that aims to influence the brain’s neuronal activity through direct application of magnetic (TMS) or electric (tDCS) energy. It is thought the combination of neuromodulation and motor training may reduce the dosage of training needed, and would promote recovery to a greater extent for more individuals. Indeed, previous work in adult stroke demonstrate a benefit of combining repetitive TMS (rTMS) and tDCS with motor training, compared to training alone. These types of synergistic interventions are just beginning to be used in children with UCP, with some preliminary data showing potential benefit.
This study aims to offer insight into the mechanisms of tDCS and lead the field toward a better understanding of how tDCS be implemented in a neurorehabilitation setting for both children and potentially adults.
Emotion regulation in the transition to adolescence
Shreya Lakhan-Pal, Graduate Student (Institute of Child Development)
Kathleen Thomas, PhD (Institute of Child Development)
The capacity to regulate one’s emotions is a critical skill that develops into adulthood. Adolescence is a period of emotional vulnerability and hypersensitivity, and is marked by a rise in the onset of affective disorders like depression and anxiety. Problems with emotion regulation (ER) are implicated in most forms of psychopathology and in decreased socioemotional health, suggesting that successful ER may be a key protective factor during adolescence. Despite its significance in psychopathology and emotional development, little is known about changes in ER in this time.
While social regulation plays an important role throughout the lifespan, evidence suggests that it becomes less effective during adolescence. Social structures and expectations are in dramatic flux, and emotions are more volatile. During stressful situations, neither parent nor friend presence effectively regulates stress hormones or emotion-related neural activity,and neural networks for self-regulation are still developing. Thus, it seems likely that there is a period of emotional vulnerability when social regulation wanes while self-regulation is still maturing. In the proposed study, I aim to address this gap by jointly examining social and self-regulation efficacy during the transition to adolescence, and by determining how the two are associated with caregiver emotional styles.
Enhanced early nutrition for preterm infants to improve neurodevelopment and minimize metabolic risk
Sara Ramel, MD (Department of Pediatrics)
Ellen Demerath, Ph.D. (Department of Public Health)
Preterm infants undergo early growth failure while in the Neonatal Intensive Care Unit (NICU) that persists for years after discharge home. This growth failure is occurring at a time of rapid brain development, and has been associated with negative long-term neurodevelopmental outcomes. In addition, early growth failure is often followed by rapid catch-up growth in childhood, which is associated with later metabolic (obesity/diabetes/hypertension) risk. Enhanced early nutrition has been associated with improved weight gain and neurodevelopment in several small observational studies, but is not routinely provided due to hesitancy surrounding possible intolerance and concern that increased nutrition will lead to increased adiposity. Lack of randomized controlled trials on this question create concern that the observed benefit of enhanced early nutrition is actually the result of confounding, whereby healthier babies are from the start inadvertently more likely to receive better nutrition, and also exhibit faster growth and better health outcomes.The overall objective of the proposal is to demonstrate the feasibility of providing increased calories and protein in the first week of life to VLBW preterm infants, and to generate pilot data on the effects of this intervention on growth and neurodevelopmental outcomes.
Event-related potentials for early detection of the cerebral form of X-linked adrenoleukodystrophy: a feasibility study
Rene Pierpont, Ph.D., L.P. (Department of Pediatrics)
Julie Eisengart, Ph.D. (Department of Pediatrics), Weston Miller, MD (Department of Pediatrics), Paul Orchard, MD (Department of Pediatrics), Michael Georgieff, MD (Department of Pediatrics)
Adrenoleukodystrophy (ALD) is a devastating childhood neurodegenerative disease for which the onset of central nervous system (CNS) involvement is unpredictable, although previous research has shown that thirty-five percent of affected boys develop clinically evident cerebral involvement (cALD) between 4-10 years of age (1). The disease is characterized by progressive cerebral demyelination and inflammation. Devastating neurological and cognitive decline is associated with cALD, with death occurring a few years following the onset of clinically-evident disease. Patients with cALD have a fairly predictable, consistent pattern of white matter disease progression. Previous studies in other at-risk populations have demonstrated the ability of scalp-recorded event-related potentials (ERPs) to detect brain functional abnormalities prior to the onset of behavioral symptomatology. Early detection of the cerebral form of ALD would revolutionize treatment outcomes for patients with this condition. Given the fairly consistent pattern of cerebral disease progression within white matter tracts, and the fact that latency of ERP components are sensitive to changes in myelination and synaptic efficiency, we hypothesize that ERPs may enable more reliable prediction of disease onset than traditional behavioral measures, for which performance may be vulnerable to non-disease influences such as fatigue or anxiety.
Alicia Kunin-Batson, PdD, LP (Department of Pediatrics), Mike Troy, PhD, LP (Children's MN - Behavioral Health)
Jerica Berge, PhD, MPH, LMFT, CRLE (Family Medicine and Community Health), Rachel Hardemann, PhD, MPH (Health Policy and Management)
The experience of discrimination and harassment due to race/ethnicity is a common and significant problem, with past studies suggesting 40-70% of people of color report such experiences. Evidence is accumulating that racism is a cause of health disparities and poor health outcomes in the United States. Most previous studies have focused on the direct experience of racism at the level of the individual and associations with adult health (e.g., hypertension, all-cause mortality). However, research also suggests that racism-related stress can also be experienced indirectly, through exposure to the prejudice and discrimination experienced by others (e.g., parent to child) and the persistence of social structures which maintain racial discrimination by fostering inequitable systems (e.g., housing, employment). Few studies have examined the impact of parent-reported discrimination and harassment on children’s health and development and even fewer of these have included measures of exposure to structural racism at the community level.
There is an urgent need to learn more about avenues to disrupt the relationship between racism-related stressors and poor health outcomes. This is particularly true in the context of the current sociopolitical climate which many have argued has created a less accepting environment for immigrants and people of color, contributing to further discrimination and harassment and compounding structural inequality already present in many social systems. Drawing from previous empirical and conceptual studies, we propose that racism-related stressors will be related to important health, mental health, and cognitive developmental outcomes, and that children’s HPA-axis regulation is impacted through exposure to racism-related stress and associated with children’s health and wellness. Parenting behaviors and skills may also be impacted by exposure to racism-related stressors and provide potentially malleable intervention targets to impact children’s stress physiology as well as children’s health and development.
Impact of the intestinal microbiome on infant neurodevelopment
Ellen Demerath, Ph.D. (Department of Epidemiology and Community Health)
Today the majority of pregnant women in the United States are either overweight or obese at conception with their offspring having greater adiposity at birth, a 2-fold greater risk of later obesity, and neonatal insulin resistance. Animal models indicate that maternal obesity may have deleterious effects on brain development in offspring. Preliminary data from our laboratory suggest that infants born to mothers with high pre-gravid BMI have altered cognitive processing of visual and audio stimuli compared to infants born to mothers with normal BMIs. Maternal obesity can also cause changes in the intestinal microbiome of offspring, both pre- and postnatally. Intestinal microbial communities are thought to affect the development immunity, metabolism, and brain function, with effects that extend across an individual’s lifespan. Our main objective is to determine how variations in microbiome signatures early in life correlate with variations in hippocampal development as indexed by ERPs. The specific aims are to 1) Examine the variation in the infant biome at one month and six months of age; and 2) Determine whether these variations are associated with poorer hippocampal-based electrophysiology outcomes and behavior, and slower myelination-dependent speed of processing not only at in the neonatal period but six months later as well.
Long-term follow-up of term survivors of hypoxic-ischemic encephalopathy: an evaluation of brain function and structure
Katie Pfister, MD (Pediatrics, Division of Neonatology)
Elizabeth Zorn, MD (Pediatrics: Division of Neonatology), Christopher Boys, PhD, LP (Department of Pediatrics), Katie Thomas, PhD (Institute of Child Development)
A prospective observational cohort study design will be used to determine whether survivors of HIE who were treated with therapeutic hypothermia have deficits in memory or executive function at age 4-5 years, and whether there are observable changes in brain structure or connectivity. MRI with diffusion tensor imaging will be used to assess brain volumes, structure, and white matter connectivity. Behavioral assessments (WPPSI-IV and NEPSY-II) and parental questionnaires (BRIEF-P) will be used to assess overall intellectual function, executive function, and memory.
Longitudinal assessment of asymptomatic congenital CMV infection in Minnesota infants identified by universal screening: what is risk of sequelae?
Mark Schleiss, MD (Department of Pediatrics)
Jed Elison, PhD (Institute of Child Development), Igor Nestrasil, MD, PhD (Department of Pediatrics), Erin Osterholm, MD (Department of Pediatrics)
Symptomatic congenital CMV (cCMV) infections are commonly encountered in clinical practice, affecting approximately 0.65% of all newborns. Such infections - in symptomatic newborns - carry a substantial risk for long-term neurodevelopmental sequelae including developmental delay, mental retardation, seizure disorders, cerebral palsy, and sensorineural hearing loss. Nucleoside antiviral therapy is associated with only modest improvements in audiological and neurodevelopmental outcomes. It is much less clear how to manage infants identified with asymptomatic cCMV infection. These infants have in the past essentially escaped clinical recognition, precisely because these children are asymptomatic at birth, and there is no universal newborn cCMV screen. However, the landscape of cCMV screening is rapidly evolving, and there is increasing interest in implementation of universal cCMV screening programs. In spite of recent progress, universal newborn screening for congenital CMV in many ways remains an area of scientific uncertainty. The optimal screening methodology remains uncertain. We don’t know if asymptomatic infants should undergo full laboratory and neuroimaging evaluations, or whether treatment of infants with asymptomatic congenital CMV with antivirals should be considered. Our proposal will conduct neurocognitive and neuroimaging studies in asymptomatic infants identified with congenital CMV infection in the context of a universal screening program to address these important areas of knowledge deficit.